糖肝煎浓缩丸对2型糖尿病合并非酒精性脂肪肝大鼠肝组织PI3K/AKT通路的影响

目的：利用2型糖尿病合并非酒精性脂肪肝模型探讨糖肝煎浓缩丸通过调控胰岛素受体-α（InsR-α）/IRS （胰岛素受体）/PI3K （磷脂酰肌醇3激酶）信号通路,改善2型糖尿病合并非酒精性脂肪肝的机制。方法：选择健康雄性Wistar大鼠进行研究,分为正常组和模型组。采用高脂高糖饲料喂养加腹腔注射30 mg·kg^-1STZ缓冲液的方法建立2型糖尿病合并非酒精性脂肪肝的动物模型。模型符合糖耐量异常的标准后,随机分为模型组,吡格列酮组（1 g·kg^-1·d^-1）,糖肝煎浓缩丸中剂量组（5.6 g·kg^-1·d^-1）和糖肝煎浓缩丸低剂量组（2.8 g·kg^-1·d^-1）。药物干预8周后,生化法检测大鼠空腹血糖、肝糖原含量,ELISA法检测大鼠空腹胰岛素、肝脏GK、G-6-Pase含量,Western-Blot法检测肝脏组织InsR-α、IRS和PI3K的蛋白表达水平,采用HE染色法观察各组大鼠肝脏组织病理切片。结果：与正常组比较,模型组大鼠空腹血糖、空腹胰岛素、GK含量显著性升高,肝糖原、G-6-Pase含量显著性降低,肝脏InsR-α、IRS和PI3-K 3种蛋白的表达含量均显著减低（P<0.01）;与模型组比较,吡格列酮组和糖肝煎浓缩丸组均能显著降低大鼠空腹血糖、空腹胰岛素、GK含量,提高肝糖原、G-6-Pase含量,增加肝脏InsR-α、IRS和PI3-K 3种蛋白的表达含量（P<0.01）;与吡格列酮组相比,糖肝煎浓缩丸中剂量组效果与之无显著差异（P>0.05）。结论：糖肝煎浓缩丸可能是通过调节InsR-α/IRS/PI3K信号通路改善2型糖尿病合并非酒精性脂肪肝大鼠的糖代谢紊乱及肝脏损伤。

Effect of Tangganjian concentrated pills on PI3K/AKT pathway of liver tissues in type 2 diabetes mellitus combined with non-alcoholic fatty liver rats

OBJECTIVE Type 2 diabetes mellitus combined with nonalcoholic fatty liver disease model is used to investigate the mechanism of improving the insulin receptor alpha (InsR-α)/IRS (insulin receptor)/PI3K (phosphatidylinositol 3 kinase) signaling pathway in liver tissues.METHODS Healthy male Wistar rats were selected and divided into normal group and model group. An animal model of type 2 diabetes mellitus complicated with nonalcoholic fatty liver was established by feeding high fat and high sugar diet with intraperitoneal injection of 30 mg·kg^-1 STZ buffer. After the model met the standard of impaired glucose tolerance, the rats were randomly divided into model group, pioglitazone group (1 g·kg^-1·d^-1), middle dose group (5.6 g·kg^-1·d^-1) and low dose group (2.8 g·kg^-1·d^-1). After 8 weeks of drug intervention, the content of fasting blood glucose (FBG) and liver glycogen were detected by biochemical process, the content of fasting insulin (Fins), GK and G-6-Pase were detected by ELISA method, the expression levels of InsR-α, IRS and PI3K protein in liver tissues were detected by Western-Blot. Pathological sections of liver tissues in rats were observed by HE staining.RESULTS Compared with the normal group, the contents of FBG, Fins and GK increased significantly, the contents of liver glycogen and G-6-Pase were significantly decreased, the expressions of InsR-α, IRS and PI3-K in the liver were significantly decreased in model group (P<0.01). Compared with the model group, the pioglitazone group and the TGJ concentration pill group significantly decreased FBG, Fins, liver glycogen and GK contents, increased the content of G-6-Pase, increased the expressions of InsR-α, IRS and PI3-K in the liver (P<0.01). Compared with the pioglitazone group, the middle dose of TGJ concentration pill group had no significant difference with it (P>0.05).CONCLUSION TGJ concentration pill may improve glucose metabolism disorder and liver injury in type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease by regulating InsR-α/IRS/PI3K signaling pathway.