左归降糖清脂方对2型糖尿病合并非酒精性脂肪性肝病MKR鼠肝组织PI3K信号通路的影响

目的:探讨以滋阴益气、活血解毒立法的左归降糖清脂方对2型糖尿病合并非酒精性脂肪性肝病MKR鼠肝组织PI3K、AKT₁、mTOR表达的影响。方法:8周龄MKR鼠按性别、空腹血糖、体质量随机分为空白组、模型组、中药组、阳性药物组;同龄C57/BL/6小鼠作为正常组;每组16只;除正常组、空白组外,其余各组小鼠高脂饲养8周。各给药组予以相应药物灌胃治疗,其中中药组予左归降糖清脂方29.6g/kg灌胃治疗8周后,以心脏采血处死各组小鼠,采用电化学法检测小鼠空腹血糖,常规生化法检测肝功能、血脂;电镜及HE染色观察肝组织形态结构及病理变化;实时荧光定量PCR或Western Blot分别检测肝组织PI3K、AKT₁、mTOR的mRNAs或蛋白表达水平。结果:与模型组比较,左归降糖清脂方具有改善2型糖尿病合并非酒精性脂肪性肝病MKR鼠肝功能,降低空腹血糖、血脂、降低肝组织PI3K、AKT₁、mTOR的表达水平(P<0.01),改善肝脏病理损伤的作用。结论:左归降糖清脂方通过降低PI3K、AKT₁、m TOR的表达水平,改善肝脏组织病理损伤。

Effects of Zuogui Jiangtang Qingzhi Recipe on expressions of PI3K signal pathway of liver tissue in MKR mice with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease

Objective:To investigate the effect of Zuogui Jiangtang Qingzhi Decoction on expression levels of PI3 K,AKT₁ and mTOR in liver tissue of MKR mice with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease(NAFLD).Methods:MKR mice aged 8 weeks were randomly divided into blank group,model group,traditional Chinese medicine group and positive drug group according to gender,fasting blood glucose and body weight.C57/BL/6 mice of the same age were served as normal group with 16 mice in each group.In addition to normal and blank groups,the rest of the mice were fed with high fat diet for 8 weeks.The traditional Chinese medicine group were treated with Zuogui Jiangtang Qingzhi Decoction(29.6 g/kg)for 8 weeks,mice in each group were sacrificed by heart blood sampling.Fasting blood glucose was detected by electrochemical method,morphological structure and pathological changes of liver tissue were observed by electron microscopy and HE.The mRNA expression levels of PI3 K,AKT₁ and mTOR were detected by real-time fluorescence quantitative PCR and the proteins were detected by Western Blot respectively.Results:Compared with the model group,Zuogui Jiangtang Qingzhi Decoction can improve liver function of MKR rats with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease,reduce fasting blood glucose,and blood lipid,reduce the expression levels of PI3 K,AKT₁ and mTOR in MKR mice with type 2 diabetes mellitus and non-alcoholic fatty liver disease(P<0.01).Conclusion:Zuogui Jiangtang Qingzhi Decoction can improve liver pathological damage of liver tissue by reducing the expression levels of PI3 K,AKT₁ and mTOR.