绞股蓝皂苷干预2型糖尿病合并非酒精性脂肪肝病的机制  

Mechanism underlying protective effect of gypenosides against type 2 diabetes mellitus and nonalcoholic fatty liver disease in rats

作　　者：雷飞飞[1] 李云静[1] 李儒贵[1] 李刚[1] 李金科[1] 李芳[1] 谭华炳[1] 

机构地区：[1]湖北医药学院附属人民医院感染性疾病科肝病研究所,湖北省十堰市442000

出　　处：《世界华人消化杂志》2016年第30期4169-4176,共8页World Chinese Journal of Digestology

基　　金：湖北省卫生厅科研项目计划,No.JX4B58

摘　　要：目的研究绞股蓝皂苷对2型糖尿病合并非酒精性脂肪性肝病(type 2 diabetes mellitus and nonalcoholic fatty liver disease,T2DMNAFLD)大鼠的作用机制.方法将60只SD大鼠随机分成5个实验组:空白对照组(Ⅰ组),T2DM-NAFLD模型组(Ⅱ组),T2DM-NAFLD模型绞股蓝皂苷(gypenosides,GPS)小剂量治疗组(Ⅲ组),T2DM-NAFLD模型GPS中剂量治疗组(Ⅳ组),T2DM-NAFLD模型GPS大剂量治疗组(Ⅴ组).肝组织病理学检查了解GPS治疗的效果,免疫组织化学分析肝组织中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),核因子-κB(nuclear factor-κB,NF-κB)表达情况,PCR对过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)和细胞色素P4501A1(cytochrome P4501A1,CYP4501A1)的mRNA表达进行定量分析.结果GPS治疗组能显著降低血糖,具有剂量依赖性.免疫组织化学分析发现,GPS治疗显著降低大鼠肝组织中细胞因子TNF-α和NF-κB的表达,并有剂量依赖关系.肝组织PCR检测发现,GPS治疗能下调肝组织PPARγ和CYP4501A1的mRNA表达.GPS治疗能减轻治疗组大鼠肝脏脂肪浸润程度,通过剂量依赖关系方式逆转脂肪肝程度.结论GPS通过下调细胞因子TNF-α、NF-κB以及PPARγ和CYP4501A1 mRNA的表达对T2DM-NAFLD大鼠肝组织产生保护作用.AIM To explore the mechanism underlying protective effect of gypenosides（GPS） against type 2 diabetes mellitus and nonalcoholic fatty liver disease（T2DM-NAFLD） in rats.METHODS Sixty rats were randomly divided into five groups：blank control group,T2DM-NAFLD model group,low dose GPS group,medium dose GPS group,and high dose GPS group.The efficacy was confirmed by histopathology,and the expression of tumor necrosis factor-α（TNF-α） and nuclear factor-κB（NF-κB） in the liver was analyzed by immunohistochemistry.In addition,the expression of peroxisome proliferator activated receptor gamma（PPARγ）and cytochrome P4501A1（CYP4501A1）mRNAs was detected by RT-PCR.RESULTS Immunohistochemical study showed that the expression of TNF-α and NF-κB was significantly reduced by GPS,in a dosedependent manner.The expression of PPARγand CYP4501A1 mRNAs measured by RTPCR was also significantly down-regulated by GPS.Moreover,GPS decreased the infiltration of liver fats and reversed the histopathological changes in a dose-dependent manner.CONCLUSION GPS protects against T2DM-NAFLD by downregulating the expression of TNF-α,NF-κB,PPARγ and CYP4501A1.

关 键 词：绞股蓝皂苷 2型糖尿病并非酒精性脂肪肝 核因子-ΚB 肿瘤坏死因子-α 过氧化物酶体增殖物激活受体Γ 细胞色素P4501A1 

分 类 号：R285[医药卫生—中药学]