In this report we studied the relationship between hydrocortisone(F) concentration and its inductive effect on tyrosine aminotransferase (TAT) activity in primary cultures of rat hepatocytes, and the regulation of rat...In this report we studied the relationship between hydrocortisone(F) concentration and its inductive effect on tyrosine aminotransferase (TAT) activity in primary cultures of rat hepatocytes, and the regulation of rat liver high- and low-affinity glucocorticoid receptors (GRH and GRL) by glucocorticoids (GC). When F concentration was 1-10 nmol/L, the dose-response relationship showed a tendency of saturation. TAT activity was much higher when F concentration was between 10 nmol/L and 10 μmol/l. When F concentration reached 10 μmol/L the induction of TAT could be completely inhibited by RU486, a competitive antagonist of GRH and GRL. These results indicate that induction of TAT by high F concentration was mediated by GRL. The concentration of GC in plasma remained over 10-6 mol/L for 3 d by subcutaneous injection of F in polyvinyl alcohol into the rats. The binding capacity (Ro) of GRH decreased significantly 1 h after injection and remained at a low level,while Ro of GRL increased at 1 h, 24 h, 48 h after injection. It may be concluded that GC could down-regulate GRH and up-regulate GRL. The pathophysiological and clinical significance of these results is discussed.展开更多
The effect of forskolin, an activator of adenylate cyclase, on glucocorticoid-induced modulation of proliferation and differentiation of a human osteosarcoma cell line(HOS-8603) was iniually studied. It was found that...The effect of forskolin, an activator of adenylate cyclase, on glucocorticoid-induced modulation of proliferation and differentiation of a human osteosarcoma cell line(HOS-8603) was iniually studied. It was found that forskolin could significantly augment展开更多
BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insuffi ciency(CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute e...BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insuffi ciency(CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).METHODS: Since January 2010 to December 2012, 385 patients, who met the criteria of AECOPD, were enrolled in the Intensive Care Unit(ICU) of the First People's Hospital and Municipal Central Hospital of Xiangtan City. The AECOPD patients complicated with CIRCI screened by an adrenalcorticotrophic hormone test within 12 hours after admission to ICU were divided into a treatment group(n=32) and a control group(n=31) for a prospective, randomized and controlled clinical trial. Hydrocortisone(150 mg/d) or normal saline was injected intravenously for 7 days. The patients were followed up for 28 days after injection. The endpoint included 28-day survival time, non-shock time, ICU stay and the period of non-mechanical ventilation. The markers ofinfl ammation C-reactive protein, tumor necrosis factor-α, interleukin 6 and procalcitonin were measured at baseline and 7 days after treatment. The variables were analyzed by Student's t test, the non-parametric statistical test, the Chi-square test or the Kaplan-Meier method with SPSS18.0 statistic software. A P value <0.05 was considered statistically signifi cant.RESULTS: Totally 63 patients were diagnosed with CIRCI by an adrenalcorticotrophic hormone test and the prevalence rate was 16.4%. The shock rate of the AECOPD patients complicated with CIRCI was higher than that of the AECOPD patients without CIRCI(23.8% vs. 8.7%, P<0.01). KaplanMeier analysis revealed that the 28-day survival time of the treatment group was obviously longer than that of the control group(P<0.05). Compared with the control group, shock-free days within 28 days was longer in the treatment group(18.2±9.5 vs. 25.8±4.1, P<0.05). Treatment with low-dose glucocorticoid obviously decreased the markers ofinfection and inflammation(P<0.01), such as C-reactive protein(13.2±5.5 mg/L vs. 8.3±3.1 mg/L for the control group; 13.5±5.9 mg/L vs. 5.1±2.3 mg/L for the treatment group), tumor necrosis factor-α(26.1±16.2 g/L vs. 17.5±11.7 g/L for the control group; 25.0±14.8 g/L vs. 10.4±7.8 g/L for the treatment group) and procalcitonin(3.88 g/L vs. 2.03 g/L for the control group; 3.77 g/L vs. 1.26 g/L for the treatment group). Furthermore, the markers in the treatment group decreased more obviously than those in the control group(P<0.01).CONCLUSION: The prevalence rate of CIRCI was higher in the patients with AECOPD in the department of critical medicine, and low-dose glucocorticoid treatment for one week reduced the 28-day mortality, shock time and markers ofinfection and infl ammation.展开更多
BACKGROUND: Community-acquired pneumonia(CAP) is pneumonia acquired infectiously from normal social contact as opposed to being acquired during hospitalization. CAP is a leading cause of illness and death. This review...BACKGROUND: Community-acquired pneumonia(CAP) is pneumonia acquired infectiously from normal social contact as opposed to being acquired during hospitalization. CAP is a leading cause of illness and death. This review aims to determine the efficacy and safety of glucocorticoids in the treatment of community-acquired pneumonia(CAP).DATA SOURCES: We searched randomized controlled trials(RCTs) from Pubmed, EMBASE, Cochrane Library, Chinese Journal Full-text Database, and Chinese Biomedical Literature Database to obtain the information by using steroids, glucocorticoids, cortisol, corticosteroids, community-acquired pneumonia and CAP as key words. The quality of RCTs was evaluated. A Meta-analysis was made using Rev Man 5.0 provided by the Cochrance Collaboration.RESULTS: Seven RCTs involving 944 patients were included in the meta-analysis. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in standard treatment group(WMD=–1.70, 95%CI 2.01–1.39, Z=10.81, P<0.00001). No statistically significant differences were found in the mortality rate(RR=0.77,95%CI 0.46–1.27, Z=1.03, P=0.30), the mean length of hospital stay in ICU(WMD=1.17, 95%CI 1.68–4.02, Z=0.81, P=0.42), the incidence of super infection(RR=1.32, 95%CI 0.66–2.63, Z=0.79, P=0.43), the incidence of hyperglycemia(RR=1.84, 95%CI 0.76–4.41, Z=1.36, P=0.17), the incidence of upper gastrointestinal bleeding(RR=1.98, 95%CI 0.37–10.59, Z=0.80, P=0.42) between the standard treatment group and the glucocorticoids treatment group.CONCLUSIONS: The use of glucocorticoids in patients with community-acquired pneumonia can significantly shorten the duration of illness and have a favorable safety profile. However, it could not reduce the overall mortality.展开更多
In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome.This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat ...In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome.This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat lung following endotoxin （LPS） induced shock. Totally 56 SD rats were randomly divided into 4 groups： LPS shock group （n=16）, LPS＋vasoactive intestinal peptide group（VIP） group, （n=16）, LPS＋VIP＋ glucocorticoid （GC） group, （n=16）,and control group （n=8）. LPS shock was induced by intravenous injection of LPS （10 mg/kg） in rats. Within 15 minutes after LPS injection, rats in the treatment groups received VIP （5 nmol/kg） or VIP and methylprednisolone （3 mg/kg）. The control group was given normal saline instead of LPS. The rats of the four groups were sacrificed at 6 hours,24 hours after injection respectively, and the lung tissues were collected. Pathological changes of the lungs were examined by light microscopy and electron microscopy. GRmRNA expression in the lung tissues was evaluated by RT-PCR. In the LPS shock group, lung histopathology demonstrated destruction of the alveolar space,widening of the inter-alveolar space, inflammatory cell infiltration and interstitial edema. However,pathological changes in the LPS＋ VIP group and LPS＋ VIP＋GC group were milder than those in the LPS shock group. Six hours after LPS injection, GR mRNA expression was down-regulated in the LPS group （0.72± 0.24） and LPS＋ VIP group （0.88±0.27） （P〈0.05） as compared with the control group （1.17±0.22）. The LPS shock group showed a more significant down-regualtion than the LPS＋VIP group, but the difference was not statistically significant （P〉0.05）. In contrast, GRmRNA expression in the LPS＋ VIP＋GC group was significantly up-regulated at 6 hours and further at 24 hours （1.45±0.32 and 1.91±0.46 respectively） （P〈0.05）. GrmRNA expression decreased in LPS induced lung injury in rats. Combined treatment with VIP and GC mitigated lung injury ang inflammation. The mechanism may be related to up-regulation of GR mRNA expression.展开更多
The changes of glucocorticoid receptor （GR） and the reactivity of target cells toglucocorticoids （GC） were studied experimentally.The results showed that GC resistance,which wascaused mainly by the decrease of GR,...The changes of glucocorticoid receptor （GR） and the reactivity of target cells toglucocorticoids （GC） were studied experimentally.The results showed that GC resistance,which wascaused mainly by the decrease of GR,developed in burned and shocked rats and dogs.Thesechanges may exacerbate the shock state,and even lead to the development of multiple organfailuue.The protection of GC against intestinal ischemic shock of dogs was demonstrated after theconcentration of dexamethasone （Dex） in plasma was elevated to 10<sup>-6</sup> mol/L by iv injection of 5mgDex/kg body weight.展开更多
BACKGROUND： Ventilator induced lung injury （VILI） is a serious complication in the treatment of mechanical ventilating patients, and it is also the main cause that results in exacerbation or death of patients. In t...BACKGROUND： Ventilator induced lung injury （VILI） is a serious complication in the treatment of mechanical ventilating patients, and it is also the main cause that results in exacerbation or death of patients. In this study, we produced VILI models by using glucocorticoid in rats with high tidal volume mechanical ventilation, and observed the content of macrophage inflammatory protein-1α （MIP-1α） in plasma and bronchoalveolar lavage fluid （BALF） and the expression of MIP-1α mRNA and nuclear factor-kappa B （NF-кB） p65 mRNA in the lung so as to explore the role of glucocorticoid in mechanical ventilation.METHODS： Thirty-two healthy Wistar rats were randomly divided into a control group, a ventilator induced lung injury （VILI） group, a dexamethasone （DEX） group and a budesonide （BUD） group. The content of MIP-1a in plasma and BALF was measured with ELISA and the level of MIP-1α mRNA and NF-кBp65 mRNA expressing in the lung of rats were detected by RT-PCR. The data were expressed as mean±SD and were compared between the groups.RESULTS： The content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the DEX and BUD groups were signifi cantly lower than those in the VILI group （P〈0.001）. Although the content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the BUD group were higher than those in the DEX group, there were no signifi cant differences between them （P〉0.05）.CONCLUSIONS： Glucocorticoid could down-regulate the expression of MIP-1α by inhibiting the activity of NF-кB in the lung and may exert preventive and therapeutic effects on VILI to some extent. The effect of local use of glucocorticoid against VILI is similar to that of systemic use, but there is lesser adverse reaction.展开更多
Objective: To investigate the effect of Calpain inhibitor I on glucocorticoid receptor-dependent proteasomal degradation and its transcriptional activity. Methods: After Raw-264.7 cells were treated with Calpain inhib...Objective: To investigate the effect of Calpain inhibitor I on glucocorticoid receptor-dependent proteasomal degradation and its transcriptional activity. Methods: After Raw-264.7 cells were treated with Calpain inhibitor I, dexamethasone, or both for about 12 h, the change of glucocorticoid receptor was detected by western blot analysis. COS-7 cells were transfected with PRsh-GRα expression vector and glucocorticoid-responsive receptor pMAMneo-CAT, then the effect of Calpain inhibitor I on glucocorticoid receptor transcriptional activation ability was determined by CAT activity. Results: The glucocorticoid receptor levels decreased after RAW-264.7 cells were treated with dexamethasone for 12 hours, which effect can be inhibited by Calpain inhibitor I to some extent. CAT activity assay showed that Calpain inhibitor I enhance glucocorticoid receptor transcriptional activity. Conclusion: Calpain inhibitor I can inhibit the down-regulation of dexamethasone on glucocorticoid receptor, and enhances glucocorticoid receptor transactivation ability.展开更多
The high-affinity glucocorticoid binding sites（HAGS）and the low-affinity glucocor-ticoid binding sites（LAGS）with steroid specificity were demonstrated in cerebral cytosol ofrats by using the radioligand binding as...The high-affinity glucocorticoid binding sites（HAGS）and the low-affinity glucocor-ticoid binding sites（LAGS）with steroid specificity were demonstrated in cerebral cytosol ofrats by using the radioligand binding assay.The equilibrium dissocation constant（Kd）of HAGSand LAGS were（2.78+0.71）×10<sup>-8</sup>mol/L and（2.12±1.06）×10<sup>-6</sup>mol/L respectively as esti-mated by Scatchard and Pseudoseatchard analysis.Glucocorticoid receptors（GR）in the trau-matized（left）hemisphere cytosol were decreased more significantly than those in both the con-trol（right）hemisphere cytosol at 6 h postinjury and normal brain tissue（P【0.05）,but Kd ofGR showed no significant changes.GR of liver cytosol at 6h postinjury were more markedly de-creased than normal hepatic cytosol,but Kd of GR underwent no significant changes.These da-ta demonstrate that high-dose glucocorticoid（GC）used in the treatment of traumatic brain ede-ma might maintain target-cell reactions by increasing the production of GC receptor complexesand is most likely to be mediated by LAGS.展开更多
The effect of glucocorticoids on the down-regulation of glucocorticoidreceptor (GR) mRNA was studied in intact rats.GR mRNA was characterized byNorthern blot hybridization and quantitated by dot blot hybridization usi...The effect of glucocorticoids on the down-regulation of glucocorticoidreceptor (GR) mRNA was studied in intact rats.GR mRNA was characterized byNorthern blot hybridization and quantitated by dot blot hybridization using a hu-man GR cDNA fragment as a probe.Administration of hydrocortisone (F) inpolyvinyl alcohol (PVA) resulted in a rapid increase in plasma glucocorticoidswhich maintained at stress levels (20 to 40μg/dl) for about 3 d.HepaticGR mRNA decreased significantly to 73.5±6.3% of control values 6h followingF treatment,after which the decline of GR mRNA was gradual,reaching a mini-mum of 44.0±5.0% of control levels 3d after the treatment.The effect of F onthe down-regulation of hepatic GR mRNA lasted up to 11 d.In contrast,F treat-ment had no effect on GR mRNA in rat brain.These results are consistent withthe changes in GR in rats as reported previously,except that even though thehepatic cytosol GR decreased markedly,no significant changes in hepatic GRmRNA were found 1h after F treatment,strongly suggesting that thedown-regulation of GR by its ligands in vivo occurs at both transcriptional andposttranscriptional levels and is of tissue-specific fashion.展开更多
The homogeneity between the high-and low-affinity glucocorticoid receptors(GR_H and GR_L)was testified by immunoaffinity chromatography using Mab N250(recognizing the immunogenic domain at the N terminal of GR_H)and M...The homogeneity between the high-and low-affinity glucocorticoid receptors(GR_H and GR_L)was testified by immunoaffinity chromatography using Mab N250(recognizing the immunogenic domain at the N terminal of GR_H)and Mab BuGR1(recognizing the DNA binding domain of GR_H).The specific binding peak of 0.98μmol/L[~3H]triamcinolone acetonide(TA)was higher than that of 52.50nmol/L[~3H]TA.The re-sult suggests that the antigenic determinants of GR_L are similar to those of GR_H.ThecDNA of rat liver GR_H was introduced into GR_H-and GR_L-negative mouse fibroblast cellline E82.A3 by calcium phosphate coprecipitation.A number of clones which expressGR_H were selected with G418(400μg/ml).The results of radioligand binding assay indicatethat GR_H gene is expressed successfully and GR_L also may be encoded by GR_H gene.展开更多
Renal and hepatic cytosol glucocorticoid receptors (GR) were measured by radio-Ligand binding assay at different stages in rats with passive Heymann nephritis(PHN) induced by the injection of antiserum against renal t...Renal and hepatic cytosol glucocorticoid receptors (GR) were measured by radio-Ligand binding assay at different stages in rats with passive Heymann nephritis(PHN) induced by the injection of antiserum against renal tubular antigen. The content of renal G展开更多
The maximal binding capacity(R0) and dissociation constant(Kd) of glucocorticoid receptors(GR) in peripheral leucocytes and the cortisol(F) level in plasma were estimated in 17 patients with bronchial asthma.The R0 of...The maximal binding capacity(R0) and dissociation constant(Kd) of glucocorticoid receptors(GR) in peripheral leucocytes and the cortisol(F) level in plasma were estimated in 17 patients with bronchial asthma.The R0 of GR was 12908+2501 sites cell which wa展开更多
Objective： To explore the effect of high dose of glucocorticoid （GC） on the synthesis of corticotropin releasing hormone （CRH） and transcription of its mRNA in hypothalamus paraventricular nuclei （PVN） in order...Objective： To explore the effect of high dose of glucocorticoid （GC） on the synthesis of corticotropin releasing hormone （CRH） and transcription of its mRNA in hypothalamus paraventricular nuclei （PVN） in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods： A total of 60 rats were divided into 5 groups： blank control, 10^-6 mol/L dexamethasone （DEX） group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group （10^-2mol/L RU486）. All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy （LCSM）; CRH mRNA level was explored by in situ hybridization. Results： 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion ： High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.展开更多
Objective: To study the effect of glucocorticoid on the promoter of the pre-receptor glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene. Methods: The 1. 2 kb length sequence u...Objective: To study the effect of glucocorticoid on the promoter of the pre-receptor glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene. Methods: The 1. 2 kb length sequence upstream to the transcription start site of the 11β-HSD1 gene was amplified with polymerase chain reaction (PCR) and then was cloned into pBLCAT6 plasmid carrying chloramphenicol acetyltransferase ( CAT) reporter gene. The plasmid pBLCAT6 carrying the promoter and reporter gene was used to transfect HeLa cells to study the regulation of 11β-HSD1 gene expression by glucocorticoids in terms of reporter gene expression. Results: PCR showed that there was a complete alignment of the amplified sequence with the sequence 1. 2 kb upstream to the transcription start site of 11β-HSD1 gene. When cloned into pBLCAT6 plasmid carrying the reporter gene, this part of the promoter is functional in terms of regulation of reporter gene expression upon transfection into HeLa cells. The synthetic glucocorticoid-dexamethasone induced the reporter gene expression in the system described above, which was blocked by glucocorticoid receptor antagonist RU486. Conclusion: Glucocorticoids can modulate the expression of 11β-HSD1 through a mechanism involving activation of GR and interaction of the promoter of 11β-HSD1 gene.展开更多
文摘In this report we studied the relationship between hydrocortisone(F) concentration and its inductive effect on tyrosine aminotransferase (TAT) activity in primary cultures of rat hepatocytes, and the regulation of rat liver high- and low-affinity glucocorticoid receptors (GRH and GRL) by glucocorticoids (GC). When F concentration was 1-10 nmol/L, the dose-response relationship showed a tendency of saturation. TAT activity was much higher when F concentration was between 10 nmol/L and 10 μmol/l. When F concentration reached 10 μmol/L the induction of TAT could be completely inhibited by RU486, a competitive antagonist of GRH and GRL. These results indicate that induction of TAT by high F concentration was mediated by GRL. The concentration of GC in plasma remained over 10-6 mol/L for 3 d by subcutaneous injection of F in polyvinyl alcohol into the rats. The binding capacity (Ro) of GRH decreased significantly 1 h after injection and remained at a low level,while Ro of GRL increased at 1 h, 24 h, 48 h after injection. It may be concluded that GC could down-regulate GRH and up-regulate GRL. The pathophysiological and clinical significance of these results is discussed.
文摘The effect of forskolin, an activator of adenylate cyclase, on glucocorticoid-induced modulation of proliferation and differentiation of a human osteosarcoma cell line(HOS-8603) was iniually studied. It was found that forskolin could significantly augment
文摘BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insuffi ciency(CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).METHODS: Since January 2010 to December 2012, 385 patients, who met the criteria of AECOPD, were enrolled in the Intensive Care Unit(ICU) of the First People's Hospital and Municipal Central Hospital of Xiangtan City. The AECOPD patients complicated with CIRCI screened by an adrenalcorticotrophic hormone test within 12 hours after admission to ICU were divided into a treatment group(n=32) and a control group(n=31) for a prospective, randomized and controlled clinical trial. Hydrocortisone(150 mg/d) or normal saline was injected intravenously for 7 days. The patients were followed up for 28 days after injection. The endpoint included 28-day survival time, non-shock time, ICU stay and the period of non-mechanical ventilation. The markers ofinfl ammation C-reactive protein, tumor necrosis factor-α, interleukin 6 and procalcitonin were measured at baseline and 7 days after treatment. The variables were analyzed by Student's t test, the non-parametric statistical test, the Chi-square test or the Kaplan-Meier method with SPSS18.0 statistic software. A P value <0.05 was considered statistically signifi cant.RESULTS: Totally 63 patients were diagnosed with CIRCI by an adrenalcorticotrophic hormone test and the prevalence rate was 16.4%. The shock rate of the AECOPD patients complicated with CIRCI was higher than that of the AECOPD patients without CIRCI(23.8% vs. 8.7%, P<0.01). KaplanMeier analysis revealed that the 28-day survival time of the treatment group was obviously longer than that of the control group(P<0.05). Compared with the control group, shock-free days within 28 days was longer in the treatment group(18.2±9.5 vs. 25.8±4.1, P<0.05). Treatment with low-dose glucocorticoid obviously decreased the markers ofinfection and inflammation(P<0.01), such as C-reactive protein(13.2±5.5 mg/L vs. 8.3±3.1 mg/L for the control group; 13.5±5.9 mg/L vs. 5.1±2.3 mg/L for the treatment group), tumor necrosis factor-α(26.1±16.2 g/L vs. 17.5±11.7 g/L for the control group; 25.0±14.8 g/L vs. 10.4±7.8 g/L for the treatment group) and procalcitonin(3.88 g/L vs. 2.03 g/L for the control group; 3.77 g/L vs. 1.26 g/L for the treatment group). Furthermore, the markers in the treatment group decreased more obviously than those in the control group(P<0.01).CONCLUSION: The prevalence rate of CIRCI was higher in the patients with AECOPD in the department of critical medicine, and low-dose glucocorticoid treatment for one week reduced the 28-day mortality, shock time and markers ofinfection and infl ammation.
文摘BACKGROUND: Community-acquired pneumonia(CAP) is pneumonia acquired infectiously from normal social contact as opposed to being acquired during hospitalization. CAP is a leading cause of illness and death. This review aims to determine the efficacy and safety of glucocorticoids in the treatment of community-acquired pneumonia(CAP).DATA SOURCES: We searched randomized controlled trials(RCTs) from Pubmed, EMBASE, Cochrane Library, Chinese Journal Full-text Database, and Chinese Biomedical Literature Database to obtain the information by using steroids, glucocorticoids, cortisol, corticosteroids, community-acquired pneumonia and CAP as key words. The quality of RCTs was evaluated. A Meta-analysis was made using Rev Man 5.0 provided by the Cochrance Collaboration.RESULTS: Seven RCTs involving 944 patients were included in the meta-analysis. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in standard treatment group(WMD=–1.70, 95%CI 2.01–1.39, Z=10.81, P<0.00001). No statistically significant differences were found in the mortality rate(RR=0.77,95%CI 0.46–1.27, Z=1.03, P=0.30), the mean length of hospital stay in ICU(WMD=1.17, 95%CI 1.68–4.02, Z=0.81, P=0.42), the incidence of super infection(RR=1.32, 95%CI 0.66–2.63, Z=0.79, P=0.43), the incidence of hyperglycemia(RR=1.84, 95%CI 0.76–4.41, Z=1.36, P=0.17), the incidence of upper gastrointestinal bleeding(RR=1.98, 95%CI 0.37–10.59, Z=0.80, P=0.42) between the standard treatment group and the glucocorticoids treatment group.CONCLUSIONS: The use of glucocorticoids in patients with community-acquired pneumonia can significantly shorten the duration of illness and have a favorable safety profile. However, it could not reduce the overall mortality.
文摘In cases of severe sepsis and septic shock, a series of pathophysiological changes lead to multiple organ dysfunction syndrome.This study aimed to investigate the expression of glucocorticoid receptor mRNA in the rat lung following endotoxin （LPS） induced shock. Totally 56 SD rats were randomly divided into 4 groups： LPS shock group （n=16）, LPS＋vasoactive intestinal peptide group（VIP） group, （n=16）, LPS＋VIP＋ glucocorticoid （GC） group, （n=16）,and control group （n=8）. LPS shock was induced by intravenous injection of LPS （10 mg/kg） in rats. Within 15 minutes after LPS injection, rats in the treatment groups received VIP （5 nmol/kg） or VIP and methylprednisolone （3 mg/kg）. The control group was given normal saline instead of LPS. The rats of the four groups were sacrificed at 6 hours,24 hours after injection respectively, and the lung tissues were collected. Pathological changes of the lungs were examined by light microscopy and electron microscopy. GRmRNA expression in the lung tissues was evaluated by RT-PCR. In the LPS shock group, lung histopathology demonstrated destruction of the alveolar space,widening of the inter-alveolar space, inflammatory cell infiltration and interstitial edema. However,pathological changes in the LPS＋ VIP group and LPS＋ VIP＋GC group were milder than those in the LPS shock group. Six hours after LPS injection, GR mRNA expression was down-regulated in the LPS group （0.72± 0.24） and LPS＋ VIP group （0.88±0.27） （P〈0.05） as compared with the control group （1.17±0.22）. The LPS shock group showed a more significant down-regualtion than the LPS＋VIP group, but the difference was not statistically significant （P〉0.05）. In contrast, GRmRNA expression in the LPS＋ VIP＋GC group was significantly up-regulated at 6 hours and further at 24 hours （1.45±0.32 and 1.91±0.46 respectively） （P〈0.05）. GrmRNA expression decreased in LPS induced lung injury in rats. Combined treatment with VIP and GC mitigated lung injury ang inflammation. The mechanism may be related to up-regulation of GR mRNA expression.
文摘The changes of glucocorticoid receptor （GR） and the reactivity of target cells toglucocorticoids （GC） were studied experimentally.The results showed that GC resistance,which wascaused mainly by the decrease of GR,developed in burned and shocked rats and dogs.Thesechanges may exacerbate the shock state,and even lead to the development of multiple organfailuue.The protection of GC against intestinal ischemic shock of dogs was demonstrated after theconcentration of dexamethasone （Dex） in plasma was elevated to 10<sup>-6</sup> mol/L by iv injection of 5mgDex/kg body weight.
文摘BACKGROUND： Ventilator induced lung injury （VILI） is a serious complication in the treatment of mechanical ventilating patients, and it is also the main cause that results in exacerbation or death of patients. In this study, we produced VILI models by using glucocorticoid in rats with high tidal volume mechanical ventilation, and observed the content of macrophage inflammatory protein-1α （MIP-1α） in plasma and bronchoalveolar lavage fluid （BALF） and the expression of MIP-1α mRNA and nuclear factor-kappa B （NF-кB） p65 mRNA in the lung so as to explore the role of glucocorticoid in mechanical ventilation.METHODS： Thirty-two healthy Wistar rats were randomly divided into a control group, a ventilator induced lung injury （VILI） group, a dexamethasone （DEX） group and a budesonide （BUD） group. The content of MIP-1a in plasma and BALF was measured with ELISA and the level of MIP-1α mRNA and NF-кBp65 mRNA expressing in the lung of rats were detected by RT-PCR. The data were expressed as mean±SD and were compared between the groups.RESULTS： The content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the DEX and BUD groups were signifi cantly lower than those in the VILI group （P〈0.001）. Although the content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the BUD group were higher than those in the DEX group, there were no signifi cant differences between them （P〉0.05）.CONCLUSIONS： Glucocorticoid could down-regulate the expression of MIP-1α by inhibiting the activity of NF-кB in the lung and may exert preventive and therapeutic effects on VILI to some extent. The effect of local use of glucocorticoid against VILI is similar to that of systemic use, but there is lesser adverse reaction.
文摘Objective: To investigate the effect of Calpain inhibitor I on glucocorticoid receptor-dependent proteasomal degradation and its transcriptional activity. Methods: After Raw-264.7 cells were treated with Calpain inhibitor I, dexamethasone, or both for about 12 h, the change of glucocorticoid receptor was detected by western blot analysis. COS-7 cells were transfected with PRsh-GRα expression vector and glucocorticoid-responsive receptor pMAMneo-CAT, then the effect of Calpain inhibitor I on glucocorticoid receptor transcriptional activation ability was determined by CAT activity. Results: The glucocorticoid receptor levels decreased after RAW-264.7 cells were treated with dexamethasone for 12 hours, which effect can be inhibited by Calpain inhibitor I to some extent. CAT activity assay showed that Calpain inhibitor I enhance glucocorticoid receptor transcriptional activity. Conclusion: Calpain inhibitor I can inhibit the down-regulation of dexamethasone on glucocorticoid receptor, and enhances glucocorticoid receptor transactivation ability.
文摘The high-affinity glucocorticoid binding sites（HAGS）and the low-affinity glucocor-ticoid binding sites（LAGS）with steroid specificity were demonstrated in cerebral cytosol ofrats by using the radioligand binding assay.The equilibrium dissocation constant（Kd）of HAGSand LAGS were（2.78+0.71）×10<sup>-8</sup>mol/L and（2.12±1.06）×10<sup>-6</sup>mol/L respectively as esti-mated by Scatchard and Pseudoseatchard analysis.Glucocorticoid receptors（GR）in the trau-matized（left）hemisphere cytosol were decreased more significantly than those in both the con-trol（right）hemisphere cytosol at 6 h postinjury and normal brain tissue（P【0.05）,but Kd ofGR showed no significant changes.GR of liver cytosol at 6h postinjury were more markedly de-creased than normal hepatic cytosol,but Kd of GR underwent no significant changes.These da-ta demonstrate that high-dose glucocorticoid（GC）used in the treatment of traumatic brain ede-ma might maintain target-cell reactions by increasing the production of GC receptor complexesand is most likely to be mediated by LAGS.
文摘The effect of glucocorticoids on the down-regulation of glucocorticoidreceptor (GR) mRNA was studied in intact rats.GR mRNA was characterized byNorthern blot hybridization and quantitated by dot blot hybridization using a hu-man GR cDNA fragment as a probe.Administration of hydrocortisone (F) inpolyvinyl alcohol (PVA) resulted in a rapid increase in plasma glucocorticoidswhich maintained at stress levels (20 to 40μg/dl) for about 3 d.HepaticGR mRNA decreased significantly to 73.5±6.3% of control values 6h followingF treatment,after which the decline of GR mRNA was gradual,reaching a mini-mum of 44.0±5.0% of control levels 3d after the treatment.The effect of F onthe down-regulation of hepatic GR mRNA lasted up to 11 d.In contrast,F treat-ment had no effect on GR mRNA in rat brain.These results are consistent withthe changes in GR in rats as reported previously,except that even though thehepatic cytosol GR decreased markedly,no significant changes in hepatic GRmRNA were found 1h after F treatment,strongly suggesting that thedown-regulation of GR by its ligands in vivo occurs at both transcriptional andposttranscriptional levels and is of tissue-specific fashion.
文摘The homogeneity between the high-and low-affinity glucocorticoid receptors(GR_H and GR_L)was testified by immunoaffinity chromatography using Mab N250(recognizing the immunogenic domain at the N terminal of GR_H)and Mab BuGR1(recognizing the DNA binding domain of GR_H).The specific binding peak of 0.98μmol/L[~3H]triamcinolone acetonide(TA)was higher than that of 52.50nmol/L[~3H]TA.The re-sult suggests that the antigenic determinants of GR_L are similar to those of GR_H.ThecDNA of rat liver GR_H was introduced into GR_H-and GR_L-negative mouse fibroblast cellline E82.A3 by calcium phosphate coprecipitation.A number of clones which expressGR_H were selected with G418(400μg/ml).The results of radioligand binding assay indicatethat GR_H gene is expressed successfully and GR_L also may be encoded by GR_H gene.
文摘Renal and hepatic cytosol glucocorticoid receptors (GR) were measured by radio-Ligand binding assay at different stages in rats with passive Heymann nephritis(PHN) induced by the injection of antiserum against renal tubular antigen. The content of renal G
文摘The maximal binding capacity(R0) and dissociation constant(Kd) of glucocorticoid receptors(GR) in peripheral leucocytes and the cortisol(F) level in plasma were estimated in 17 patients with bronchial asthma.The R0 of GR was 12908+2501 sites cell which wa
文摘Objective： To explore the effect of high dose of glucocorticoid （GC） on the synthesis of corticotropin releasing hormone （CRH） and transcription of its mRNA in hypothalamus paraventricular nuclei （PVN） in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods： A total of 60 rats were divided into 5 groups： blank control, 10^-6 mol/L dexamethasone （DEX） group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group （10^-2mol/L RU486）. All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy （LCSM）; CRH mRNA level was explored by in situ hybridization. Results： 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion ： High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.
基金Supported by the National Natural Science Foundation of China(No.39970285),Shanghai Science and Technology Development Project(No.99JC14036)
文摘Objective: To study the effect of glucocorticoid on the promoter of the pre-receptor glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene. Methods: The 1. 2 kb length sequence upstream to the transcription start site of the 11β-HSD1 gene was amplified with polymerase chain reaction (PCR) and then was cloned into pBLCAT6 plasmid carrying chloramphenicol acetyltransferase ( CAT) reporter gene. The plasmid pBLCAT6 carrying the promoter and reporter gene was used to transfect HeLa cells to study the regulation of 11β-HSD1 gene expression by glucocorticoids in terms of reporter gene expression. Results: PCR showed that there was a complete alignment of the amplified sequence with the sequence 1. 2 kb upstream to the transcription start site of 11β-HSD1 gene. When cloned into pBLCAT6 plasmid carrying the reporter gene, this part of the promoter is functional in terms of regulation of reporter gene expression upon transfection into HeLa cells. The synthetic glucocorticoid-dexamethasone induced the reporter gene expression in the system described above, which was blocked by glucocorticoid receptor antagonist RU486. Conclusion: Glucocorticoids can modulate the expression of 11β-HSD1 through a mechanism involving activation of GR and interaction of the promoter of 11β-HSD1 gene.
