二甲双胍对2型糖尿病大鼠非酒精性脂肪性肝病相关慢性炎症反应的影响  

Effect of metformin on chronic inflammation associated with non-alcoholic fatty liver in type 2 diabetes mellitus rats

作　　者：蔡凤[1] 刘钜荣 范德美 沈静雪[1] CAI Feng, LIU Jurong, FAN Demei, SHEN Jingxue.(Center Hospital Affiliated to Shenyang Medical College, Shenyang 110000, Chin)

机构地区：[1]沈阳医学院附属中心医院,沈阳110000

出　　处：《实用医学杂志》2018年第12期1965-1969,共5页The Journal of Practical Medicine

基　　金：沈阳市科学技术局项目(编号:F14-158-9-29)

摘　　要：目的探讨二甲双胍(Met)对2型糖尿病(T2DM)大鼠非酒精性脂肪性肝病(NAFLD)相关的肝功、慢性炎症及肝纤维化的影响。方法建立4组大鼠模型:对照组(A组)、T2DM组(B组)、T2DM+NAFLD组(C组)、T2DM+NAFLD+Met组(D组)。造模结束后,取血及肝组织,检测肝功、C反应蛋白(CRP)等指标,ELISA法检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)等水平,评估其胰岛素抵抗情况;采用HE染色、油红O染色、Masson染色及网状纤维染色法检测肝脏的病理改变,免疫组化法检测肝组织TNF-α、IL-6及CRP表达情况。结果 (1)B、C组胰岛素抵抗及肝功异常程度均高于A组,D组低于C组。(2)B、C组炎症因子水平均高于A组,D组低于C组。(3)肝病理检测结果示,C组肝脏存在明显的脂肪变、脂肪性炎变及纤维化改变,D组较C组改善。结论二甲双胍具有改善2型糖尿病合并非酒精性脂肪性肝病相关的胰岛素抵抗、肝功异常、慢性炎症及肝脏纤维化的作用,其机制可能与降低炎症因子的表达、改善慢性炎症状态有关。Objective To investigate the effects of metformin（Met）on liver function,chronic inflammationand liver fibrosis in rats with type 2 diabetes mellitus（T2 DM）combined with nonalcoholic fatty liver disease（NAFLD）. Methods 4 groups of rat models were established：the control group（group A）,T2 DM group（groupB）,T2 DM ＋ NAFLD group（group C）and T2 DM ＋ NAFLD ＋ Met group（group D）. After grouping,the specimensof blood and liver tissues were taken. Serum liver function,C-reactive protein（CRP）,tumor necrosis factor-α（TNF-α）and interleukin-6（IL-6）were detected,and then their insulin resistance was assessed. The pathologicalchanges of the liver were detected by HE staining,oil red O staining,Masson staining and reticular fiber staining,and the expression of TNF-α,IL-6 and CRP in liver tissue was detected by immunohistochemistry. Results（1）The degree of insulin resistance and hypohepatia in group B and C were higher than those in group A,and those ofgroup D were lower than those in group C.（2）The levels of inflammatory cytokines in group B and C were higherthan those in group A,and the level in group D were lower than those in group C.（3）The pathological examinationof liver showed that there was significant fatty degeneration,fatty inflammation and fibrosis in the livers of groupC,and group D was better than those in group C. Conclusions Met is effective in the improvement of insulin resis-tance,hypohepatia,chronic inflammation and liver fibrosis in type 2 diabetes mellitus associated with non-alco-holic fatty liver disease,which in mechanism may be related to the decreased expression of inflammatory factors andimproved chronic inflammatory state.

关 键 词：二甲双胍 2型糖尿病 非酒精性脂肪性肝病 细胞因子 

分 类 号：R575.5[医药卫生—消化系统]