Objective:In recent years,the incidence and detection rate of pancreatic cystic lesions(PCLs)have increased significantly.Endoscopic ultrasound(EUS)plays an indispensable role in the diagnosis and differential diagnos...Objective:In recent years,the incidence and detection rate of pancreatic cystic lesions(PCLs)have increased significantly.Endoscopic ultrasound(EUS)plays an indispensable role in the diagnosis and differential diagnosis of PCLs.However,evidence comparing the diagnostic performance of EUS-guided fine-needle aspiration(EUS-FNA)and fine-needle biopsy(FNB)remains limited.This study aims to compare the diagnostic yield,adequacy of tissue acquisition,and safety between EUS-FNA and EUS-FNB in evaluating PCLs to inform clinical practice.Methods:A retrospective review was conducted on patients with PCLs who underwent either EUS-FNA or EUS-FNB between January 2014 and August 2021.The diagnostic yield,tissue acquisition adequacy,and incidence of adverse events were compared between the 2 groups.Results:A total of 90 patients with PCLs were included(52 in the FNA group and 38 in the FNB group).The diagnostic yield was similar between the FNA and FNB groups(94.2%vs 94.7%,P>0.05).The adequacy of tissue acquisition was 71.2%in the FNA group and 81.6%in the FNB group(P>0.05).No statistically significant difference was observed in the incidence of adverse events between the 2 groups(P>0.05).Conclusion:Both EUS-FNA and EUS-FNB demonstrate equally high diagnostic yields and tissue adequacy in PCLs,with excellent safety profiles.Both methods are safe and effective diagnostic tools for evaluating PCLs.展开更多
OBJECTIVE Pancreatic ductal adenocarcinoma(PDAC),a lethal cancer in need of new,effective therapies,has a unique tumor microenvironment characterized by a dense fibrotic stroma(desmoplasia)that is generated by pancrea...OBJECTIVE Pancreatic ductal adenocarcinoma(PDAC),a lethal cancer in need of new,effective therapies,has a unique tumor microenvironment characterized by a dense fibrotic stroma(desmoplasia)that is generated by pancreatic cancer-associated fibroblasts(PCAFs)derived from pancreatic stellate cells(PSCs)and pancreatic fibroblasts(PFs).METHEDS and RESULTS Hypothesizing that G protein-coupled receptors(GPCRs)may regulate PCAFs,we used an unbiased GPCRomic array approach to compare GPCR expression in PCAFs,PFs and PSCs and identified 82 GPCRs commonly expressed by PCAFs derived from primary tumors of five PDAC patients.We discovered that PCAFs have increased expression of numerous GPCRs,in particular a GPCR with much higher expression in PCAFs compared to both PFs and PSCs.Immunohistochemistry revealed increased expression of this GPCR in PDAC tumors.Co-culture of PSCs with PDAC cells or incubation with TNFαinduced its expression.Activation of the GPCR in PCAF sincreased expression of interleukin-6(IL-6)via a cA MP/PKA/CREB signaling pathway.GPCR knockdown with siR NA diminished IL-6 production and secretionby PCAFs and ability of PCAF conditioned media to enhance proliferation of PDAC cells.CONCLUSION We conclude that PDAC cells induce expression by PCAFs of a novel GPCR,resulting in increased IL-6 production by PCAFs and promotion of PDAC cell proliferation.This PCAF-expressed GPCR thus contributes to PDAC cell-PCAF interaction and as such,may be a novel therapeutic target for PDAC tumors.展开更多
OBJECTIVE We previously showed that human pancreatic stellate cells(HPSCs)promote pancreatic ductal adenocarcinoma(PDAC)cell growth by activating nuclear factor erythroid2-related factor 2(Nrf2),a key transcriptional ...OBJECTIVE We previously showed that human pancreatic stellate cells(HPSCs)promote pancreatic ductal adenocarcinoma(PDAC)cell growth by activating nuclear factor erythroid2-related factor 2(Nrf2),a key transcriptional regulator of cytoprotective genes.We aim to investigate whether Nrf2-mediated metabolic reprogramming and reactive oxygen species(ROS)detoxification are involved in HPSCs-mediated cell growth.METHODS Nrf2-mediated metabolic genes expression of pentose phosphate pathway(PPP)for purine nucleotide synthesis;glutamine metabolism for nicotinamide adenine dinucleotide phosphate(NADPH)-equivalent producers and also glutathione biosynthesis both for intracellular ROS inactivation were examined using quantitative real-time PCR(qRT-PCR)after treated with conditioned media derived from HPSCs(HPSC-CM)in human PDAC cells(BxPC-3and AsPC-1)with or without Nrf2 gene silencing using siRNA-mediated technique.Metabolites involved in PPP for purine nucleotide and NADPH generation were selected and their concentration was measured using UHPLC-MS/MS.Antioxidants,tiron and N-acetylcysteine(NAC)were used to attenuate the intracellular ROS rendered by Nrf2 before measuring PDAC cell growth and also phosphorylation of extracellular signal-regulated kinase(ERK)1/2and protein kinase B(AKT)using MTT and Western blotting,respectively.RESULTS Metabolically,HPSC-CMupregulated Nrf2-mediated genes involved in three metabolic pathways(G6PD,PGD,TKT,PPAT,MTHFD2,ME1,IDH1,GCLC and GCLM)in BxPC-3and AsPC-1cells.HPSC-CM was able to upregulate all the metabolic genes after Nrf2 gene silencing,and also significantly increased the metabolite concentration of ribose 5-phosphate and inosine 5′-monophosphate,which are involved in nucleotide synthesis for cell growth.Decreasing the intracellular ROS rendered by Nrf2 suppressed PDAC cell growth and also phosphorylation of ERK 1/2and AKT protein.CONCLUSION Our findings reveal that HPSC-CM activates Nrf2-mediated metabolic reprogramming,which leads to purine nucleotide synthesis and ROS detoxification to promote PDAC cell growth.展开更多
OBJECTIVE To evaluate the anticancer activity of andrographolide(AGP)and its semisynthetic analogues(SRJ09and SRJ23)in pancreatic adenocarcinoma(PDAC)cell lines harbouring therapeutically highly relevant oncogenic K-r...OBJECTIVE To evaluate the anticancer activity of andrographolide(AGP)and its semisynthetic analogues(SRJ09and SRJ23)in pancreatic adenocarcinoma(PDAC)cell lines harbouring therapeutically highly relevant oncogenic K-ras glycine-12(KRAS-G12)mutant proteins.In a landmark publication,we revealed that AGP and its derivatives bind KRAS protein to inhibit RAS signaling PNAS,110:10201-06).This discovery prompted the initiation of this investigation.METHODS The cell growth inhibitory effect of the compounds on PDAC cell lines〔PANC-1(KRAS-G12D),Capan-2(KRAS-G12V),and MIA PaCa-2(KRASG12C)〕,was assessed by MTT assay.RESULTS In comparison with AGP and SRJ09,SRJ23 showed the greatest growth inhibition in all PDAC cell lines with mutant KRAS proteins.The inhibitory effect of SRJ23 on the cell growth was similar for all PDAC cell lines.AGP exerted selective growth inhibition against PANC-1(KRAS-G12D)cells,while the growth inhibition of SRJ09 was selective towards Capan-2(KRAS-G12V)cells.CONCLUSION AGP and SRJ09 showed selectivity for PDAC cell lines with specific KRAS mutations.This suggests the mutational status of KRAS protein and the structural features of these two compounds orchestrally determined the magnitude of cell growth inhibition in PDAC cell lines.The higher potency of SRJ23 implies it could be developed into an anticancer agent for the treatment of mutant KRAS-driven malignancies.To this end,efforts are in progress to derive new molecules from this compound for further improvement of potency.展开更多
The purpose of this study was to establish a method for the rapid detection of infectious pancreatic necrosis virus(IPNV,Jasper serotype)using reverse transcription loop-mediated isothermal amplification(RT-LAMP).Four...The purpose of this study was to establish a method for the rapid detection of infectious pancreatic necrosis virus(IPNV,Jasper serotype)using reverse transcription loop-mediated isothermal amplification(RT-LAMP).Four groups of specific primers were designed,according to the genome sequence of a Chinese IPNV isolate ChRtm213.The results showed that primer set B2 had the best amplification effect.When the final concentration of Mg2+was 6 mmol·L-1,dNTPs were 1 mmol·L-1 and betaine was 0.4 mol·L-1,the reaction could be completed in a 63℃water bath within 60 min.This RT-LAMP assay for the detection of IPNV had no cross-reactivity with infectious hematopoietic necrosis virus,viral hemorrhagic septicemia virus,grass carp reovirus and spring viremia of carp virus.The detection limit was 3.2×10-12 ng·μL-1.The sensitivity of this method was 10-fold higher than that of a previously published RT-LAMP assay for detecting the Spajarup(Sp)serotype of IPNV.This method,aimed at detecting IPNV isolates that were currently prevalent in China,possessed the characteristics of strong specificity,high sensitivity and direct interpretation by the naked eyes.The IPNV RT-LAMP was successfully applied to determine the clinical samples,which indicated the IPNV RT-LAMP assay was suitable for the rapid and large-scale detections of IPNV in China.展开更多
Forsythiaside was obtained by using macro reticular resin D 101 and vaccum liquid chromatography.Using the method of agarose diffusion,the inhibition of porcine pancreatic elastase by forsythiaside was studied.The res...Forsythiaside was obtained by using macro reticular resin D 101 and vaccum liquid chromatography.Using the method of agarose diffusion,the inhibition of porcine pancreatic elastase by forsythiaside was studied.The results shown that forsythiaside could inhibit the activity of porcine pancreatic elastase.展开更多
G protein-coupled receptors(GPCRs)are the most widely targeted class for approved drugs but only a small portion(-15%)of GPCRs are currently targeted.Work in my laboratory has tested the hypothesis that individual cel...G protein-coupled receptors(GPCRs)are the most widely targeted class for approved drugs but only a small portion(-15%)of GPCRs are currently targeted.Work in my laboratory has tested the hypothesis that individual cell types express previously unrecognized GPCRs that regulate cell function and may be novel drug targets.A key focus has been our efforts to define differential expression(DE)of GPCRs on normal cells versus cells from patients with diseases:pulmonary arterial smooth muscle cells/pulmonary arterial hypertension,lung and cardiac fibroblasts/lung and cardiac fibrosis and pancreatic cells/pancreatic ductal adenocarcinoma(PDAC).To test our hypothesis,we have used unbiased(GPCRomic)approaches(Taqman GPCR arrays and RNA-seq),mining of publicly available datasets(the GTEX database for normal tissues and the Cancer Genome Atlas,TCGA)and studies of signaling and functional activity to validate newly detected GPCRs.The GPCRomic studies reveal that most cell types and tissues express>100 different GPCRs with limited prior data for many highly expressed GPCRs,numerous of which are"orphans"(which lack known physiologic agonists).Numerous GPCRs have DE and alter functionin diseased cells.For example,studies of PDAC tumors/cells and pancreatic cancer-associated fibroblasts(PCAFs)identify two GPCRs with high DE,respectively,in PDAC cells compared to normal pancreatic ductal epithelial cells and in PCAFs compared to normal pancreatic Fs/stellate cells.These two GPCRs:(1)are frequently,highly expressed in PDAC tumors compared to normal pancreas and(2)regulate functional activities that influence the malignant phenotype.Overall,the results indicate the utility of unbiased GPCRomic and data-mining approaches to identify previously unrecognized,functional GPCRs that may contribute to human disease and that may be novel,drug gable targets.展开更多
AIM:To establish a one-stage model of experimental acute necrotizing pancreatitis(ANP)in rats characterized by the simplicity of performance and a high degree of repeatability.METHODS:ANP modeling in rats was performe...AIM:To establish a one-stage model of experimental acute necrotizing pancreatitis(ANP)in rats characterized by the simplicity of performance and a high degree of repeatability.METHODS:ANP modeling in rats was performed based on modification of the ligation model as follows:synthetic material ligature using an atraumatic needle was performed to capture pancreatic gland ducts and marginal duodenum vessels.Ligature tips were exteriorized to the abdominal wall,and the ligature was skinned over to avoid catching intestine loops.Pancreatic macroscopic appearance and histological changes were observed.Blood biochemical and hemostatic indicators were also determined.RESULTS:Laboratory analysis of rats with experimental ANP showed a pattern of disturbances similar to that observed during pancreatic necrosis in humans as soon as the first day.General blood analysis revealed enhanced leukocytosis and alterations in leukogram characteristics,indicating acute inflammation.Serum levels of amylase,aspartate aminotransferase and creatinine significantly increased(P<0.05).Hemostatic indicators showed alterations indicating formation of disseminated intravascular coagulation,and signs of endotoxicosis were observed.These typical pancreatic necrosis patterns of disturbances were validated by the results of histological investigation.CONCLUSION:Histological changes and laboratory indicators confirm the development of a suitable model of ANP.展开更多
Objective:To investigate the effect of salvia miltiorrhiza on expression of the MMP-2、9 and TIMP-1、TIMP-2 in tissue of acute lung injury of severe acute pancreatitis(SAP).Methods:MMP-2、9 expression and changes of t...Objective:To investigate the effect of salvia miltiorrhiza on expression of the MMP-2、9 and TIMP-1、TIMP-2 in tissue of acute lung injury of severe acute pancreatitis(SAP).Methods:MMP-2、9 expression and changes of the lung were measured after the SAP rats were induced by retrograde injection of 5%sodium tauocholate into hepatopancreatic duct.The changes of those parameters were also measured after salvia miltiorrhiza was injected intramuscularly just after induction of SAP.Results:The level of MMP-2、9 in pancreas and lung in SAP group were significantly higher than those in sham;The level of MMP-2、9 in salvia miltiorrhiza group were significantly lower than those in SAP group. Conclusion:MMP-2、9 were overexpressed in Acute lung injury (ALI) induced by SAP, salvia miltiorrhiza downregulates MMP-2、9 expression and decreased injury of lung tissue.展开更多
基金supported by the Special Project for the Construction of Innovative Provinces in Hunan Province,China(2020SK2013)。
文摘Objective:In recent years,the incidence and detection rate of pancreatic cystic lesions(PCLs)have increased significantly.Endoscopic ultrasound(EUS)plays an indispensable role in the diagnosis and differential diagnosis of PCLs.However,evidence comparing the diagnostic performance of EUS-guided fine-needle aspiration(EUS-FNA)and fine-needle biopsy(FNB)remains limited.This study aims to compare the diagnostic yield,adequacy of tissue acquisition,and safety between EUS-FNA and EUS-FNB in evaluating PCLs to inform clinical practice.Methods:A retrospective review was conducted on patients with PCLs who underwent either EUS-FNA or EUS-FNB between January 2014 and August 2021.The diagnostic yield,tissue acquisition adequacy,and incidence of adverse events were compared between the 2 groups.Results:A total of 90 patients with PCLs were included(52 in the FNA group and 38 in the FNB group).The diagnostic yield was similar between the FNA and FNB groups(94.2%vs 94.7%,P>0.05).The adequacy of tissue acquisition was 71.2%in the FNA group and 81.6%in the FNB group(P>0.05).No statistically significant difference was observed in the incidence of adverse events between the 2 groups(P>0.05).Conclusion:Both EUS-FNA and EUS-FNB demonstrate equally high diagnostic yields and tissue adequacy in PCLs,with excellent safety profiles.Both methods are safe and effective diagnostic tools for evaluating PCLs.
文摘OBJECTIVE Pancreatic ductal adenocarcinoma(PDAC),a lethal cancer in need of new,effective therapies,has a unique tumor microenvironment characterized by a dense fibrotic stroma(desmoplasia)that is generated by pancreatic cancer-associated fibroblasts(PCAFs)derived from pancreatic stellate cells(PSCs)and pancreatic fibroblasts(PFs).METHEDS and RESULTS Hypothesizing that G protein-coupled receptors(GPCRs)may regulate PCAFs,we used an unbiased GPCRomic array approach to compare GPCR expression in PCAFs,PFs and PSCs and identified 82 GPCRs commonly expressed by PCAFs derived from primary tumors of five PDAC patients.We discovered that PCAFs have increased expression of numerous GPCRs,in particular a GPCR with much higher expression in PCAFs compared to both PFs and PSCs.Immunohistochemistry revealed increased expression of this GPCR in PDAC tumors.Co-culture of PSCs with PDAC cells or incubation with TNFαinduced its expression.Activation of the GPCR in PCAF sincreased expression of interleukin-6(IL-6)via a cA MP/PKA/CREB signaling pathway.GPCR knockdown with siR NA diminished IL-6 production and secretionby PCAFs and ability of PCAF conditioned media to enhance proliferation of PDAC cells.CONCLUSION We conclude that PDAC cells induce expression by PCAFs of a novel GPCR,resulting in increased IL-6 production by PCAFs and promotion of PDAC cell proliferation.This PCAF-expressed GPCR thus contributes to PDAC cell-PCAF interaction and as such,may be a novel therapeutic target for PDAC tumors.
基金The project supported by University of Malaya HIR/MOHE/MED-12(Chung)
文摘OBJECTIVE We previously showed that human pancreatic stellate cells(HPSCs)promote pancreatic ductal adenocarcinoma(PDAC)cell growth by activating nuclear factor erythroid2-related factor 2(Nrf2),a key transcriptional regulator of cytoprotective genes.We aim to investigate whether Nrf2-mediated metabolic reprogramming and reactive oxygen species(ROS)detoxification are involved in HPSCs-mediated cell growth.METHODS Nrf2-mediated metabolic genes expression of pentose phosphate pathway(PPP)for purine nucleotide synthesis;glutamine metabolism for nicotinamide adenine dinucleotide phosphate(NADPH)-equivalent producers and also glutathione biosynthesis both for intracellular ROS inactivation were examined using quantitative real-time PCR(qRT-PCR)after treated with conditioned media derived from HPSCs(HPSC-CM)in human PDAC cells(BxPC-3and AsPC-1)with or without Nrf2 gene silencing using siRNA-mediated technique.Metabolites involved in PPP for purine nucleotide and NADPH generation were selected and their concentration was measured using UHPLC-MS/MS.Antioxidants,tiron and N-acetylcysteine(NAC)were used to attenuate the intracellular ROS rendered by Nrf2 before measuring PDAC cell growth and also phosphorylation of extracellular signal-regulated kinase(ERK)1/2and protein kinase B(AKT)using MTT and Western blotting,respectively.RESULTS Metabolically,HPSC-CMupregulated Nrf2-mediated genes involved in three metabolic pathways(G6PD,PGD,TKT,PPAT,MTHFD2,ME1,IDH1,GCLC and GCLM)in BxPC-3and AsPC-1cells.HPSC-CM was able to upregulate all the metabolic genes after Nrf2 gene silencing,and also significantly increased the metabolite concentration of ribose 5-phosphate and inosine 5′-monophosphate,which are involved in nucleotide synthesis for cell growth.Decreasing the intracellular ROS rendered by Nrf2 suppressed PDAC cell growth and also phosphorylation of ERK 1/2and AKT protein.CONCLUSION Our findings reveal that HPSC-CM activates Nrf2-mediated metabolic reprogramming,which leads to purine nucleotide synthesis and ROS detoxification to promote PDAC cell growth.
基金The project supported by Ministry of Education,Malaysia(Research University Grant Scheme Grant 04-02-12-2017RUFundamental Research Grant Scheme Grant 04-02-13-1324FR)
文摘OBJECTIVE To evaluate the anticancer activity of andrographolide(AGP)and its semisynthetic analogues(SRJ09and SRJ23)in pancreatic adenocarcinoma(PDAC)cell lines harbouring therapeutically highly relevant oncogenic K-ras glycine-12(KRAS-G12)mutant proteins.In a landmark publication,we revealed that AGP and its derivatives bind KRAS protein to inhibit RAS signaling PNAS,110:10201-06).This discovery prompted the initiation of this investigation.METHODS The cell growth inhibitory effect of the compounds on PDAC cell lines〔PANC-1(KRAS-G12D),Capan-2(KRAS-G12V),and MIA PaCa-2(KRASG12C)〕,was assessed by MTT assay.RESULTS In comparison with AGP and SRJ09,SRJ23 showed the greatest growth inhibition in all PDAC cell lines with mutant KRAS proteins.The inhibitory effect of SRJ23 on the cell growth was similar for all PDAC cell lines.AGP exerted selective growth inhibition against PANC-1(KRAS-G12D)cells,while the growth inhibition of SRJ09 was selective towards Capan-2(KRAS-G12V)cells.CONCLUSION AGP and SRJ09 showed selectivity for PDAC cell lines with specific KRAS mutations.This suggests the mutational status of KRAS protein and the structural features of these two compounds orchestrally determined the magnitude of cell growth inhibition in PDAC cell lines.The higher potency of SRJ23 implies it could be developed into an anticancer agent for the treatment of mutant KRAS-driven malignancies.To this end,efforts are in progress to derive new molecules from this compound for further improvement of potency.
基金Supported by the National Natural Science Foundation of China(31802345)China Postdoctoral Science Foundation(2018M630893)Heilongjiang Province Postdoctoral Science Foundation(LBH-Z18275)。
文摘The purpose of this study was to establish a method for the rapid detection of infectious pancreatic necrosis virus(IPNV,Jasper serotype)using reverse transcription loop-mediated isothermal amplification(RT-LAMP).Four groups of specific primers were designed,according to the genome sequence of a Chinese IPNV isolate ChRtm213.The results showed that primer set B2 had the best amplification effect.When the final concentration of Mg2+was 6 mmol·L-1,dNTPs were 1 mmol·L-1 and betaine was 0.4 mol·L-1,the reaction could be completed in a 63℃water bath within 60 min.This RT-LAMP assay for the detection of IPNV had no cross-reactivity with infectious hematopoietic necrosis virus,viral hemorrhagic septicemia virus,grass carp reovirus and spring viremia of carp virus.The detection limit was 3.2×10-12 ng·μL-1.The sensitivity of this method was 10-fold higher than that of a previously published RT-LAMP assay for detecting the Spajarup(Sp)serotype of IPNV.This method,aimed at detecting IPNV isolates that were currently prevalent in China,possessed the characteristics of strong specificity,high sensitivity and direct interpretation by the naked eyes.The IPNV RT-LAMP was successfully applied to determine the clinical samples,which indicated the IPNV RT-LAMP assay was suitable for the rapid and large-scale detections of IPNV in China.
文摘Forsythiaside was obtained by using macro reticular resin D 101 and vaccum liquid chromatography.Using the method of agarose diffusion,the inhibition of porcine pancreatic elastase by forsythiaside was studied.The results shown that forsythiaside could inhibit the activity of porcine pancreatic elastase.
基金supported by NIH grants(R21CA202608,R21AG053568)Dept of Defense Grant(W81XWH-14-1-0372)+1 种基金Bristol Myers Squibb,Padres Pedal the Cause PTC2017an ASPET-David Lehr Research Award
文摘G protein-coupled receptors(GPCRs)are the most widely targeted class for approved drugs but only a small portion(-15%)of GPCRs are currently targeted.Work in my laboratory has tested the hypothesis that individual cell types express previously unrecognized GPCRs that regulate cell function and may be novel drug targets.A key focus has been our efforts to define differential expression(DE)of GPCRs on normal cells versus cells from patients with diseases:pulmonary arterial smooth muscle cells/pulmonary arterial hypertension,lung and cardiac fibroblasts/lung and cardiac fibrosis and pancreatic cells/pancreatic ductal adenocarcinoma(PDAC).To test our hypothesis,we have used unbiased(GPCRomic)approaches(Taqman GPCR arrays and RNA-seq),mining of publicly available datasets(the GTEX database for normal tissues and the Cancer Genome Atlas,TCGA)and studies of signaling and functional activity to validate newly detected GPCRs.The GPCRomic studies reveal that most cell types and tissues express>100 different GPCRs with limited prior data for many highly expressed GPCRs,numerous of which are"orphans"(which lack known physiologic agonists).Numerous GPCRs have DE and alter functionin diseased cells.For example,studies of PDAC tumors/cells and pancreatic cancer-associated fibroblasts(PCAFs)identify two GPCRs with high DE,respectively,in PDAC cells compared to normal pancreatic ductal epithelial cells and in PCAFs compared to normal pancreatic Fs/stellate cells.These two GPCRs:(1)are frequently,highly expressed in PDAC tumors compared to normal pancreas and(2)regulate functional activities that influence the malignant phenotype.Overall,the results indicate the utility of unbiased GPCRomic and data-mining approaches to identify previously unrecognized,functional GPCRs that may contribute to human disease and that may be novel,drug gable targets.
基金Supported by a Special Research Grant for interdisciplinary projects between the Institute of Immunology and Physiology and the Institute of Organic Synthesis,the Ural Branch of Russian Academy of Sciences(2009-2012)
文摘AIM:To establish a one-stage model of experimental acute necrotizing pancreatitis(ANP)in rats characterized by the simplicity of performance and a high degree of repeatability.METHODS:ANP modeling in rats was performed based on modification of the ligation model as follows:synthetic material ligature using an atraumatic needle was performed to capture pancreatic gland ducts and marginal duodenum vessels.Ligature tips were exteriorized to the abdominal wall,and the ligature was skinned over to avoid catching intestine loops.Pancreatic macroscopic appearance and histological changes were observed.Blood biochemical and hemostatic indicators were also determined.RESULTS:Laboratory analysis of rats with experimental ANP showed a pattern of disturbances similar to that observed during pancreatic necrosis in humans as soon as the first day.General blood analysis revealed enhanced leukocytosis and alterations in leukogram characteristics,indicating acute inflammation.Serum levels of amylase,aspartate aminotransferase and creatinine significantly increased(P<0.05).Hemostatic indicators showed alterations indicating formation of disseminated intravascular coagulation,and signs of endotoxicosis were observed.These typical pancreatic necrosis patterns of disturbances were validated by the results of histological investigation.CONCLUSION:Histological changes and laboratory indicators confirm the development of a suitable model of ANP.
基金supported mainly by Chinese traditionalmedicines and drugs administrative agent(92B093)
文摘Objective:To investigate the effect of salvia miltiorrhiza on expression of the MMP-2、9 and TIMP-1、TIMP-2 in tissue of acute lung injury of severe acute pancreatitis(SAP).Methods:MMP-2、9 expression and changes of the lung were measured after the SAP rats were induced by retrograde injection of 5%sodium tauocholate into hepatopancreatic duct.The changes of those parameters were also measured after salvia miltiorrhiza was injected intramuscularly just after induction of SAP.Results:The level of MMP-2、9 in pancreas and lung in SAP group were significantly higher than those in sham;The level of MMP-2、9 in salvia miltiorrhiza group were significantly lower than those in SAP group. Conclusion:MMP-2、9 were overexpressed in Acute lung injury (ALI) induced by SAP, salvia miltiorrhiza downregulates MMP-2、9 expression and decreased injury of lung tissue.
