NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF-β信号通路与Ⅱ型糖尿病临床相关性研究  

A study on the relationship between NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF-βsignal pathway and 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] 

机构地区：[1]重庆市涪陵中心医院心血管内科,重庆涪陵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：《西部医学》2018年第3期335-340,346,共7页Medical Journal of West China

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NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF-β信号通路与初诊Ⅱ型糖尿病(T2DM)的临床相关性。方法入选符合纳入标准的健康对照组30例及T2DM组40例,收集所有研究对象的一般临床资料,采用RTqPCR检测各组患者外周单个核细胞(PBMCs)中核苷酸结合寡聚化结构域样受体蛋白3(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,并采用ELISA法测定各组患者空腹血浆白介素-1β(IL-1β)、白介素-18(IL-18)、转化生长因子-β(TGF-β)水平。结果 PBMCs中NLRP3、凋亡相关微粒蛋白(ASC)、半胱氨酸蛋白酶-1(caspase-1)mRNA表达水平在T2DM组和对照组之间无显著性差异(P>0.05),但ASCmRNA在T2DM组与总胆固醇(TC)呈正相关(P<0.05);Caspase-1mRNA在T2DM组与体重指数(BMI)呈正相关(P<0.05)。PBMCs中NLRP3、ASC、Caspase-1表达水平及血浆IL-1β、IL-18、TGF-β水平在T2DM组和对照组之间有显著性差异(P<0.05),且ASC在T2DM组与平均动脉压(MAP)、空腹血糖(FPG)、TC、IL-1β、IL-18呈正相关(P<0.05);Caspase-1在T2DM组与吸烟、FPG、低密度脂蛋白胆固醇(LDL-C)、IL-1β呈正相关(P<0.05);IL-1β在T2DM组与TGF-β呈正相关(P<0.05)。结论以NLRP3炎性小体为中心的NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF-β信号通路可能在初诊T2DM的发生发展过程中发挥重要作用。Objective To investigate the relationship between NLRP3-ASC-Caspase-1IL-18/IL-1β-TGFβ signal pathway and newly diagnosed type 2 diabetes mellitus （T2DM）. Methods 30 controls and 40 T2DM were recruited according to the inclusion criteria. The general clinical data were collected for analysis. The expression levels of the nucleotidebinding oligomerization domainlike receptor protein 3（NLRP3） inflammasome mRNA in peripheral blood mononuclear cells （ PBMCs ） in all the groups were detected by RT-qPCR，and the expression levels of their protein were investigated by western blot. Fasting plasma interleukin1β（IL-1β）, interleukin-18（IL-18） and transforming growth factor（TGF） in all the groups were detected by ELISA assay. Results The expression levels of the NLRP3, apoptosisassociated specklike protein containing CARD （ASC） and Caspase1mRNA in PBMCs had no significant difference between T2DM group and control group （P＞0.05），while ASC mRNA were positively correlated with total cholesterol（TCH） in T2DM group （P＜0.05）, Caspase-1mRNA were positively correlated with body mass index（BMI）in T2DM group （P＜0.05）. The expression levels of the NLRP3, ASC, Caspase-1 in PBMCs and fasting plasma IL-1β,IL18, TGFβ in T2DM group were significantly higher than those in the control group （P＜0.05）, and ASC were positively correlated with mean arterial pressure（MAP），fasting plasma glucose（FPG）, TC, IL-1β and IL-18 in T2DM group（P＜0-05）. Caspase-1 were positively correlated with smoking history, FPG, low density lipoprotein cholesterol（LDLC） and IL-1β in T2DM group （P＜0.05）. IL-1β were positively correlated with TGF in T2DM group （P＜0.05）. Conclusions NLRP3-ASC-Caspase-1IL-18/IL-1β-TGFβsignal pathway centered on the NLRP3 inflammasome may play an important role in the occurrence and development of newly diagnosed T2DM.

关 键 词：NLRP3炎性小体 Ⅱ型糖尿病 白细胞介素-18 白细胞介素-1β 转化生长因子 β 

分 类 号：R587.1[医药卫生—内分泌]