NLRP3炎性小体与初诊2型糖尿病的临床相关性  

Relationship between NLRP3 inflammasome and newly diagnosed type 2 diabetes mellitus

作　　者：胡龙江[1] 周音频[1] 曹运兰 吕湛[3] 蓝运竞[1] 宁琳[1] 向立权[1] 肖鹏[1] HU Long-jiang;ZHOU Yin-pin;CAO Yun-lan;LYU Zhan;LAN Yun-jing;NING Lin;XIANG Li-quan;XIAO Peng(Department of Cardiology, Fuling Central Hospital of Chongqing City, Chongqing 408000, Chin)

机构地区：[1]重庆市涪陵中心医院心血管内科,重庆408000 [2]贵州省人民医院心血管内科,贵州贵阳550002 [3]川北医学院附属医院心血管内科,四川南充637000

出　　处：《中国临床研究》2018年第4期481-485,共5页Chinese Journal of Clinical Research

基　　金：重庆市卫生计生委医学科研项目(2015MSXM138);重庆涪陵区科技计划项目(FLKJ 2014ABB2104)

摘　　要：目的探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体与初诊2型糖尿病(T2DM)的临床相关性。方法选择2016年1月至2017年6月健康体检者30例为对照组及内分泌科初诊的40例T2DM患者为T2DM组,收集所有研究对象的性别、年龄、吸烟史、体质指数(BMI)、平均动脉压(MAP)、空腹血糖(FPG)、糖化血红蛋白(Hb A1c)、血脂等临床资料,采用实时荧光定量聚合酶链反应技术检测两组对象外周单个核细胞(PBMCs)中NLRP3炎性小体各组分mRNA的表达水平,Western blot法检测其蛋白表达水平,酶联免疫吸附试验测定空腹血浆白细胞介素(IL)-1β、IL-18水平。应用SPSS20.0软件进行统计分析。结果 PBMCs中NLRP3、凋亡相关微粒蛋白(ASC)、半胱氨酸天冬氨酸蛋白酶(Caspase)-1 mRNA表达水平在T2DM组和对照组之间无统计学差异(P均>0.05),但三者蛋白表达水平及血浆IL-1β、IL-18水平在T2DM组和对照组之间差异有统计学意义(P<0.05,P<0.01)。Spearman相关分析显示,在T2DM组,ASC与MAP(r=0.465,P=0.039)、FPG(r=0.626,P=0.003)、总胆固醇(TC,r=0.564,P=0.010)、IL-1β(r=0.502,P=0.024)、IL-18(r=0.480,P=0.032)分别呈正相关;Caspase-1与吸烟(r=0.546,P=0.013)、FPG(r=0.585,P=0.007)、低密度脂蛋白胆固醇(LDL-C,r=0.662,P=0.010)、IL-1β(r=0.624,P=0.003)分别呈正相关。结论初诊T2DM患者PBMCs来源的NLRP3炎性小体各组分蛋白表达的增加及NLRP3炎性小体的活化会促进血浆IL-1β和IL-18等炎性因子的分泌,可能在血糖代谢紊乱致T2DM的发生、发展过程中起重要作用。高血压、高血糖、高TC、高LDL-C、吸烟是激活NLRP3炎性小体的重要危险因素。Objective To investigate the correlation of nucleotides binding oligomeric domain like receptor protein 3（NLRP3） inflammasome with newly diagnosed type 2 diabetes mellitus（T2DM）. Methods Thirty healthy subjects for physical examination（control group） and 40 T2DM patients（T2DM group） conforming to the inclusion criteria were selected. The clinical data including sex,age,smoking history,body mass index（BMI）,mean artery pressure（MAP）,fasting plasma glucose（FPG）,glycosylated hemoglobin（HbA1c） and blood lipids in all research objects were collected. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to respectively detect the expression levels of mRNAs and proteins of components of NLRP3 inflammasome in peripheral blood mononuclear cells（PBMCs）. Enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of fasting plasma interleukin（IL）-1β and IL-18. SPSS20. 0 software was used for making statistical analysis. Results There were no significant differences in mRNAs expression levels of NLRP3,apoptosis-associated speck-like protein containing CARD domain（ASC） and cysteine aspartase-1（Caspase-1） in PBMCs between T2DM group and control group（all P〈0. 05）,but there were significant differences in expression levels of NLRP3,ASC and Caspase-1 proteins in PBMCs along with the levels of plasma IL-1β and IL-18 between T2DM group and control group（P〈0. 05,P〈0. 01）. Spearman correlation analysis showed that ASC protein were positively correlated with MAP（r = 0. 465,P = 0. 039）,FPG（r = 0. 626,P = 0. 003）,total cholesterol（TC,r =0. 564,P = 0. 010）,IL-1β（r = 0. 502,P = 0. 024） and IL-18（r = 0. 480,P = 0. 032）,respectively in T2DM group.Caspase-1 protein were positively correlated with smoking（r = 0. 546,P = 0. 013）,FPG（r = 0. 585,P = 0. 007）,low density lipoprotein cholesterol（LDL-C,0. 662,P = 0. 010） and IL-1β（0. 624（P = 0. 003）,respectively in T2DM group.Co

关 键 词：核苷酸结合寡聚化结构域样受体蛋白3 炎性小体 2型糖尿病 白细胞介素-18 白细胞介素-1Β 

分 类 号：R587.1[医药卫生—内分泌]