糖脂毒性诱导胰岛β细胞炎症因子过表达的研究  

Overexpression of inflammatory cytokines in pancreatic beta cells induced by glucolipotoxicity

作　　者：胡朝恩 钟大鹏[2] 艾智华[2] HU Chaoen;ZHONG Dapeng;AI Zhihua(Department of Intensive Care Unit,Init Panzhihua Central Hospital,Panzhihua,Sichuan 617000,China;Department of Endocrinology,Chengdu Military General Hospital,Chengdu,Sichuan 610083,China)

机构地区：[1]四川省攀枝花市中心医院重症医学科,617000 [2]成都军区总医院内分泌科,成都610083

出　　处：《检验医学与临床》2018年第12期1716-1719,共4页Laboratory Medicine and Clinic

基　　金：四川省卫生和计划生育委员会资助项目(2012JY0030)

摘　　要：目的了解高糖、高脂环境对胰岛β细胞功能和Toll受体3(TLR3)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、C反应蛋白(CRP)、补体C3及补体C4表达的影响。方法培养小鼠胰岛β细胞株(NIT-1)经高糖高脂刺激后,应用CCK-8试剂盒检测细胞增殖情况,采用实时荧光定量聚合酶链反应(RT-PCR)检测TLR3mRNA的表达,采用酶联免疫吸附试验(ELISA)检测细胞培养上清液中TNF-α、IL-1β、IL-6、CRP、补体C3及补体C4的表达。结果高糖高脂刺激后,胰岛β细胞增殖被抑制,TLR3mRNA、TNF-α、IL-1β、IL-6、CRP、补体C3及补体C4的表达明显增加;并且高糖高脂(GZ)组胰岛β细胞损伤和炎症因子过表达程度明显高于高糖(G)组和高脂(Z)组,差异均有统计学意义(P<0.05)。结论高糖高脂可能通过激活TLR3信号通路等途径产生大量炎症因子和免疫因子,抑制胰岛β细胞增殖,导致胰岛β细胞功能障碍,并且糖、脂协同作用明显大于单独的糖、脂毒性。Objective This study was designed to investigate the effects of high glucose and high fat environment on the function of isletβ-cell and expression of Toll receptor 3（TLR3）,tumor necrosis factor-α（TNF-α）,interleukin-1β（IL-1β）,interleukin 6（IL-6）,C-reactive protein（CRP）,complement C3 and complement C4.Methods The cultured isletβcell line（NIT-1）was stimulated by high glucose and high fat,and the cell proliferation was detected by CCK-8 method,TLR3 mRNA expression was detected by real time fluorescence quantitative polymerase chain reaction（RT-PCR）and the levels of TNF-α,IL-1β,IL-6,CRP,complement C3 and complement C4 in cell culture supernatant were detected by enzyme-linked immunosorbent assay（ELISA）.Results The proliferation of islet beta cells was inhibited after high glucose and high fat stimulation,however,the expression of TLR3 mRNA,TNF-α,IL-1β,IL-6,CRP,complement C3 and complement C4 were increase significantly.The extent of isletβcell damage and over-expression of inflammatory cytokines were significantly higher in high glucose and lipid（GZ）group than those in high glucose（G）group or high fat（Z）group（P〈0.05）.Conclusion High glucose and high lipid may produce a large number of inflammatory factors and immune factors through the activation of TLR3 signaling pathway,inhibit the proliferation of islet beta cells and lead to islet beta cell dysfunction,and the synergistic effect of sugar and fat is significantly greater than that of individual glucose and lipid toxicity.

关 键 词：糖脂毒性 胰岛Β细胞功能障碍 炎症因子 慢性炎症 

分 类 号：R446.11[医药卫生—诊断学]