OBJECTIVE To investigate the role of transient receptor potential melastatin 2(TRPM2),a calcium-permeable non-selective cation channel which acts as an oxidative stress sensor,in mediating the production of pro-inflam...OBJECTIVE To investigate the role of transient receptor potential melastatin 2(TRPM2),a calcium-permeable non-selective cation channel which acts as an oxidative stress sensor,in mediating the production of pro-inflammatory IL-1βin high glucose condition.METHODS Human pro-monocytic leukemia cell U937 was purchased from ATCC and cultured in RPMI 1640(Life Technologies).Prior to high glucose(HG)stimulation,U937 cells were cultured in medium with glucose 5.5mmol·L-1 for 48 h.The cells were then incubated in high glucose concentration(30mmol·L-1)or mannitol(30mmol·L-1)for 48 h.The protein expression of TRPM2 and the production of human IL-1β were evaluated by ELISA.TRPM2 inhibitors(DPQ and AMP)and TRPM2 siRNAs were employed to further investigate the role of TRPM2 in HG-induced IL-1β production.RESULTS The TRPM2 protein expression was significantly up-regulated by 2-folds in U937 cells after the treatment of high glucose(30mmol·L-1 for 48h)(P<0.01).The production of IL-1β in U937 was also significantly increased by HG treatment and was time-and dose-dependent(10,20 or 30mmol·L-1 glucose for 24,48 or 72h)(P<0.01).The HG-induced IL-1β production in U937 could be abolished by using TRPM2 inhibitors DPQ(100μmol·L-1 for 45min)and AMP(100μmol·L-1 for 45 min)as well as by the transfection of TRPM2siRNAs(60nmol·L-1).CONCLUSION High glucose condition(such as in diabetes)might mediate pro-inflammatory environments via the modulation of TRPM2 channels on immune cells.展开更多
基金The project supported by Science and Technology Development Fund of Macao SAR(118/2012/A)Research Committee of the University of Macao〔MYRG124(Y1-L3)-ICMS12-HPM〕
文摘OBJECTIVE To investigate the role of transient receptor potential melastatin 2(TRPM2),a calcium-permeable non-selective cation channel which acts as an oxidative stress sensor,in mediating the production of pro-inflammatory IL-1βin high glucose condition.METHODS Human pro-monocytic leukemia cell U937 was purchased from ATCC and cultured in RPMI 1640(Life Technologies).Prior to high glucose(HG)stimulation,U937 cells were cultured in medium with glucose 5.5mmol·L-1 for 48 h.The cells were then incubated in high glucose concentration(30mmol·L-1)or mannitol(30mmol·L-1)for 48 h.The protein expression of TRPM2 and the production of human IL-1β were evaluated by ELISA.TRPM2 inhibitors(DPQ and AMP)and TRPM2 siRNAs were employed to further investigate the role of TRPM2 in HG-induced IL-1β production.RESULTS The TRPM2 protein expression was significantly up-regulated by 2-folds in U937 cells after the treatment of high glucose(30mmol·L-1 for 48h)(P<0.01).The production of IL-1β in U937 was also significantly increased by HG treatment and was time-and dose-dependent(10,20 or 30mmol·L-1 glucose for 24,48 or 72h)(P<0.01).The HG-induced IL-1β production in U937 could be abolished by using TRPM2 inhibitors DPQ(100μmol·L-1 for 45min)and AMP(100μmol·L-1 for 45 min)as well as by the transfection of TRPM2siRNAs(60nmol·L-1).CONCLUSION High glucose condition(such as in diabetes)might mediate pro-inflammatory environments via the modulation of TRPM2 channels on immune cells.
文摘目的探讨应激性高血糖比值(stress hyperglycemia ratio,SHR)对非糖尿病急性大血管闭塞性脑卒中血管内治疗(endovascular treatment,EVT)成功再通后症状性脑出血(symptomatic intracerebral hemorrhage,sICH)及预后的预测价值。方法选取2022年6月至2024年6月衡水市人民医院收治的非糖尿病急性大血管闭塞性脑卒中患者150例,均行EVT并获得成功再通。根据患者术后24 h是否发生sICH分为sICH组15例和非sICH组135例;又根据患者术后3个月预后分为预后不良组55例和预后良好组95例。分析所有患者的一般临床资料,采用多因素logistic回归分析非糖尿病急性大血管闭塞性脑卒中EVT成功再通后患者sICH及预后的影响因素,采用ROC曲线分析SHR对非糖尿病急性大血管闭塞性脑卒中EVT成功再通后sICH及预后的预测价值。结果sICH组栓塞型闭塞(66.67%vs 37.04%)、入院时美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分[(20.15±3.68)分vs(15.62±3.10)分]、SHR显著高于非sICH组(1.25±0.25 vs 1.01±0.28),差异有统计学意义(P<0.05,P<0.01)。预后不良组女性(49.09%vs 29.47%)、年龄[(75.41±5.38)岁vs(172.56±5.63)岁]、入院时NIHSS评分[(18.65±3.71)分vs(16.27±3.21)分]、既往脑卒中(32.73%vs 14.74%)、SHR(1.16±0.23 vs 1.02±0.25)显著高于预后良好组(P<0.05,P<0.01)。多因素logistic回归分析显示,闭塞类型(OR=2.038,95%CI:1.138~4.234,P=0.000)、入院时NIHSS评分(OR=2.026,95%CI:1.173~4.317,P=0.000)、SHR(OR=1.996,95%CI:1.101~4.027,P=0.000)是非糖尿病急性大血管闭塞性脑卒中EVT成功再通后患者发生sICH的危险因素。多因素logistic回归分析显示,性别(OR=2.004,95%CI:1.085~3.407,P=0.000)、年龄(OR=2.075,95%CI:1.138~4.067,P=0.000)、入院时NIHSS评分(OR=2.010,95%CI:1.208~4.106,P=0.000)、既往脑卒中(OR=2.034,95%CI:1.137~4.821,P=0.000)、SHR(OR=2.038,95%CI:1.138~4.234,P=0.000)是非糖尿病急性大血管闭塞性脑卒中EVT成功再通后患者预后不良的危险因素。ROC曲线分析显示,SHR预测非糖尿病急性大血管闭塞性脑卒中EVT成功再通后患者发生sICH及预后不良的敏感性分别为80.00%、81.82%,特异性分别为82.22%、80.00%,曲线下面积分别为0.797、0.823。结论SHR可影响非糖尿病急性大血管闭塞性脑卒中EVT成功再通后患者的sICH及预后,且SHR对非糖尿病急性大血管闭塞性脑卒中EVT成功再通后患者发生sICH及预后不良具有一定的预测价值。
