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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 nucleotide binding oligomerization domain-like receptor protein 3 (ILRP3) inflammasome in type 2 diabetes mellitus complicated with coronary heart disease. Methods A total of 130 inpatients with cardiovascular diseases at Xinqiao Hospital of the Third Military Medical University were enrolled and divided into three groups: simple coronary heart disease (n = 40), simple type 2 diabetes mellitus (n = 20), type 2 diabetes complicated with coronary heart disease n = 40) and normal control group (n = 30). Peripheral blood mononuclear cells and plasma were isolated. RT-q PCR and Western blot were used to detect the expression of NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1 in peripheral blood mononuclear cells The mRNA and protein expression of IL-1β in plasma were detected by ELISA. Results The mRNA and protein expressions of NLRP3, ASC, Caspase-1 in peripheral blood mononuclear cells of coronary heart disease group, simple type 2 diabetes mellitus group and type 2 diabetes mellitus complicated with coronary heart disease group were significantly higher than those of normal control group (P <0.05) Among them, the expression of ASC and Caspase-1 mRNA in peripheral blood mononuclear cells in patients with type 2 diabetes complicated with coronary heart disease was significantly higher than that in patients with simple coronary heart disease and type 2 diabetes mellitus (P <0.05), while type 2 diabetes complicated with coronary heart disease The expression of NLRP3 protein in peripheral blood mononuclear cells was significantly higher than that in simple coronary heart disease group and simple type 2 diabetes group (P <0.05). At the same time, the levels of IL-1βin plasma of patients with coronary heart disease, simple type 2 diabetes mellitus and type 2 diabetes complicated with coronary heart disease were (24.05 ± 1.00), (22.86 ± 1.66), (26.85 ± 1.45) ng / L (12.53 ± 2.79) ng / L were significantly higher than those in normal control group (P <0.05). The level of IL-1β in type 2 diabetic patients with coronary heart disease was significantly higher than those in patients with simple coronary heart disease and type 2 diabetes mellitus Group (P <0.05). Conclusion The abnormal activation of NLRP3 inflammasome can promote the occurrence and development of type 2 diabetes mellitus complicated with coronary heart disease, which may become a new target of prevention and treatment of type 2 diabetes mellitus complicated by coronary heart disease.