二甲双胍对非酒精性脂肪性肝病大鼠肝组织T-钙黏蛋白表达的影响

Effects of metformin on expressions of T-cadherin in the liver tissues of rats with non-alcoholic fatty liver disease

目的探讨二甲双胍对非酒精性脂肪性肝病(NAFLD)大鼠肝组织T-钙黏蛋白表达的影响,为临床研究提供参考。方法雄性SD大鼠40只随机分组,NC1组:8周正常饮食组;NC2组:16周正常饮食组;HFD1组:8周高脂饮食组;HFD2组:16周高脂饮食组;HFD+M组:二甲双胍治疗组,即16周高脂饮食同时给予二甲双胍治疗8周。免疫组化法和实时荧光定量PCR法检测各组大鼠肝组织T-钙黏蛋白的蛋白和mRNA表达水平。结果 HFD+M组大鼠肝组织的NAFLD活动度评分(NAS)较HFD2组明显降低(P<0.01),T-钙黏蛋白的蛋白和mRNA表达亦明显下降(P<0.05)。肝组织T-钙黏蛋白表达的免疫组化评分与肝组织的炎症分级、脂肪变百分比和气球样变程度均呈正相关(P<0.01)。结论二甲双胍可能通过下调肝组织T-钙黏蛋白的表达发挥对NAFLD的治疗作用。

Objective To investigate the hepatic expressions of T-cadherin and effects of metformin on expressions of T-cadherin in rats with non-alcoholic fatty liver disease(NAFLD). Methods Forty male Sprague-Dawley rats were randomly divided into 5 groups:rats in NC1 group were fed a normal diet for eight weeks;rats in NC2 group were fed a normal diet for sixteen weeks;rats inHFD1 group were fed a high-fat diet for eight weeks;rats in HFD2 groupwere fed a high-fat diet for sixteen weeks;rats inHFD+M group were fed a high-fat diet for sixteen weeks and treated with metformin for eight weeks. T-cadherin protein expression levels in liver tissues were detected with immunohistochemistry, and the T-cadherin mRNA expression levels in livers were detected with fluorescent quantitative PCR. Results Compared with HFD2 group, NAFLD active score(NAS) of the liver tissue in the HFD+M group was significantly decreased(P<0.01), and T-cadherinprotein and mRNA expression levels in HFD + M group were significantly decreased(P<0.05). The immunohistochemistry scores of the T-cadherin in the liver tissues were positively related to the grade of inflammation, percentage of fat and ballooning degeneration(P<0.01). Conclusion Metformin treatment alleviates the histological lesions of NAFLD and may play the therapeutic effect on NAFLD by down-regulating the expression of T-cadherin in the liver tissue.