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NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF信号通路与Ⅱ型糖尿病临床相关性研究
胡龙江,周音频,曹运兰,吕湛,蓝运竞,宁琳,向立权,肖鹏
0
(重庆市涪陵中心医院心血管内科,重庆 涪陵 408000;贵州省人民医院心血管内科,贵州 贵阳 550002;川北医学院附属医院心血管内科)
摘要:
目的 探讨NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF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RTqPCR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(TGF)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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信号通路可能在初诊T2DM的发生发展过程中发挥重要作用。
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
DOI:
基金项目: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)
A study on the relationship between NLRP3-ASC-Caspase-1-IL-18/IL-1-TGF signal pathway and diagnosed type 2 diabetes mellitus
HU Longjiang,ZHOU Yinpin,CAO Yunlan,LV Zhan,LAN Yunjing,NING Lin,XIANG Liquan,XIAO Peng
(Department of Cardiology,Fuling Center Hospital of Chongqing City,Fuling 408000, Chongqing, China;Department of Cardiology, Guizhou Provincial People's Hospital, Guiyang 550002, China;Department of Cardiology,The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000,Sichuan, China)
Abstract:
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.
Key words:  NLRP3 inflammasome  Type 2 diabetes  Interleukin-1β  Interleukin-18  Transforming growth factor

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