核苷酸结合寡聚化结构域样受体蛋白3炎性体在2型糖尿病并发冠心病过程中的作用  

Role of nucleotide binding oligomerization domain-like receptor protein 3 inflammasome in occurrence of coronary heart disease in patients with type 2 diabetes mellitus

作　　者：曹运兰 胡龙江[2] 宋耀明[1] 

机构地区：[1]第三军医大学新桥医院心血管内科、全军心血管病研究所,重庆400038 [2]重庆市涪陵中心医院心血管内科,重庆408000

出　　处：《第三军医大学学报》2017年第8期801-806,共6页Journal of Third Military Medical University

基　　金：重庆市卫生计生委医学科研资助面上项目(2015XMSB000312)~~

摘　　要：目的探究核苷酸结合寡聚化结构域样受体蛋白3(nucleotide binding oligomerization domain-like receptor protein 3,NLRP3)炎性体在2型糖尿病并发冠心病过程中的作用。方法选取第三军医大学新桥医院心血管内科的住院患者共130例,分为单纯冠心病组(n=40)、单纯2型糖尿病组(n=20)、2型糖尿病并发冠心病组(n=40)及正常对照组(n=30)。分离外周血单个核细胞及血浆。采用RT-q PCR、Western blot分别检测各组外周血单个核细胞中NLRP3、凋亡相关斑点样蛋白(apoptosisassociated speck-like protein,ASC)、半胱天冬氨酸蛋白酶-1(caspase-1)mRNA及蛋白表达情况,ELISA法检测各组血浆中IL-1β含量。结果单纯冠心病组、单纯2型糖尿病组及2型糖尿病并发冠心病组外周血单个核细胞中NLRP3、ASC、Caspase-1 mRNA及蛋白表达水平均较正常对照组显著增高(P<0.05),其中,2型糖尿病并发冠心病组ASC、Caspase-1 mRNA在外周血单个核细胞中的表达显著高于单纯冠心病组及单纯2型糖尿病组(P<0.05),而2型糖尿病并发冠心病组NLRP3蛋白在外周血单个核细胞中的表达显著高于单纯冠心病组及单纯2型糖尿病组(P<0.05)。同时,测得单纯冠心病组、单纯2型糖尿病组及2型糖尿病并发冠心病组血浆中IL-1β含量分别为(24.05±1.00)、(22.86±1.66)、(26.85±1.45)ng/L,较正常对照组(12.53±2.79)ng/L均显著升高(P<0.05),其中,2型糖尿病并发冠心病组血浆中IL-1β含量显著高于单纯冠心病组及单纯2型糖尿病组(P<0.05)。结论 NLRP3炎性体的异常激活可促进2型糖尿病并发冠心病病理过程的发生、发展,其可能成为防治2型糖尿病并发冠心病的新靶点。Objective To investigate the role of inflammasome of nucleotide binding oligomerization domainlike receptor protein 3 （NLRP3） in the occurrence of coronary heart disease （CHD） in patients with type 2 diabetes mellitus （T2DM）. Methods One hundred and thirty patients hospitalized in the Department of Cardiology, Xinqiao Hospital between March and August 2016 were enrolled in this study, including 40 with CHD, 20 with T2DM group, and 40 with T2DM complicated by CHD, with 30 individuals without T2DM or CHD serving as the control group. Peripheral blood monocytes （HPBMCs） and plasma were collected from the subjects to detect the transcription and protein levels of NLRP3, apoptosis-associated speck-like protein （ASC） and caspase-1 using real-time qPCR and Western blotting; the plasma level of IL-1β was detected with enzyme-linked immunosorbent assay （ELISA）. Results Both the mRNA and protein levels of NLRP3, ASC and caspase-1 in the HPBMCs were significantly increased in patients with CHD, T2DM and T2DM complicated by CHD groups as compared with the control group （P〈0.05）. HPBMCs from diabetic patients with CHD patients showed significantly higher ASC and caspase-1 mRNA levels and NLRP3 protein level than those from CHD or T2DM patients （P〈0.05）. The mean plasma levels of IL-1β were 24.05±1.00, 22.86±1.66, and 26.85±1.45 ng/L in CHD, T2DM and T2DM complicated by CHD groups, respectively, all significantly higher than the level in the control group （12.53±2.79 ng/L, P〈0.05）. Conclusion The aberrant activation of NLRP3 inflammasome promotes the occurrence of CHD in patients with T2DM and may serve as a new target for prevention and treatment of the CHD in diabetic patients.

关 键 词：核苷酸结合寡聚化结构域样受体蛋白3 炎性体 冠心病 2型糖尿病 IL-1Β 

分 类 号：R341[医药卫生—基础医学] R587.1