硫辛酸对高糖诱导的肾小球系膜细胞NLRP3炎症小体表达的影响  

Effect of lipoic acid on the expression of NLRP3 inflammasome in glomerular mesangial cells induced by high glucose

作　　者：冯颖 赵淑敏 王中英[1] 刘艳 FENG Ying;ZHAO Shumin;WANG Zhongying;LIU Yan(Department of Internal Medicine Teaching and Research Office,Heze Medical College,Shandong Province,Heze 274000,China;Department of Endocrinology,Affiliated Hospital of Heze Medical College,Shandong Province,Heze 274000,China)

机构地区：[1]菏泽医学专科学校内科教研室,山东菏泽274000 [2]菏泽医学专科学校附属医院内分泌科,山东菏泽274000

出　　处：《中国当代医药》2022年第5期5-8,共4页China Modern Medicine

基　　金：山东省医药卫生科技发展计划项目(2019WS 348);菏泽医学专科学校科研项目(H18K10)。

摘　　要：目的观察高血糖对培养的人肾小球系膜细胞(HMC)中NLRP3炎症小体表达的影响,并探讨硫辛酸(LA)对上述过程的干预机制,以探寻糖尿病肾病(DN)发病新机制和防治新策略。方法传代培养人HMC,根据不同的干预因素分为正常对照(NG)组、高糖(HG)组、LA组、HG+LA组。采用CCK-8方法分别检测不同浓度的LA对HMC活性的影响,流式细胞仪检测活性氧(ROS)水平,RT-PCR检测NLRP3炎症小体mRNA的表达,Western-blot检测LA对HMC中NLRP3炎症小体的蛋白表达的影响。结果CCK-8结果显示,LA的最佳保护浓度为200μmol/l;流式细胞仪检测结果显示,HG组ROS表达水平高于NG组,差异有统计学意义(P<0.05)。RT-PCR及Western-blot检测结果显示,HG组NLRP3炎症小体表达高于NG组,差异有统计学意义(P<0.05);加入LA后,NLRP3炎症小体的表达均下降,差异有统计学意义(P<0.05)。结论高糖环境可促进人HMC的增殖,在一定浓度范围内,适当浓度的LA能抑制HMC的增殖;高血糖可通过氧化应激途径增加NLRP3炎症小体的表达,影响DN的发生发展,而LA对以上过程具有抑制作用。Objective To observe the effect of hyperglycemia on the expression of NLRP3 inflammasome in cultured human glomerular mesangial cells(HMC),and to explore the intervention mechanism of lipoic acid(LA)on the above process,so as to explore the new pathogenesis and prevention strategies of diabetic nephropathy(DN).Methods Human HMC was subcultured and divided into normal control group(NG),high glucose group(HG),LA group and HG^(^(+))LA group according to different intervention factors.CCK-8 detects the effects of different concentrations of LA on HMC activity.Flow cytometry detects the level of reactive oxygen species(ROS),RT-PCR detects the expression of NLRP3 inflammasomes,and Western-blot detects the effect of LA on the protein expression of NLRP3 inflammasomes in HMC.Results CCK-8 results showed that the optimal protective concentration of LA was 200μmol/L.The expression level of ROS in the HG group was higher than that in the NG group as detected by flow cytometry,and the difference was statistically significant(P<0.05).RT-PCR and Western-blot test results showed that the expression of NLRP3 inflammasome in the HG group was higher than that in the NG group,and the difference was statistically significant(P<0.05).After adding LA,the expression of NLRP3 inflammasome decreased,and the difference was statistically significant(P<0.05).Conclusion A high glucose environment can promote the proliferation of HMC.Within a certain concentration range,lipoic acid at an appropriate concentration can inhibit the proliferation of HMC;hyperglycemia can increase the expression of NLRP3 inflammasomes through oxidative stress and affect the occurrence and development of diabetic nephropathy.The lipoic acid has an inhibitory effect on the above process.

关 键 词：糖尿病肾病 肾小球系膜细胞 NLRP3炎症小体 硫辛酸 

分 类 号：R587.2[医药卫生—内分泌]