大柴胡汤调控PI3K/AKT/AQP9信号通路改善2型糖尿病合并非酒精性脂肪性肝病糖脂代谢紊乱OA

Objective:To explore the mechanism of Dachaihu Decoction in improving glucose and lipid metabolism disorders in rats with type 2 diabetes mellitus(T2DM)complicated by non-alcoholic fatty liver disease(NAFLD).Methods:Healthy male Wistar rats were randomly divided into the normal group(n=6,fed a regular diet)and the modeling group(fed a 1135DM-type high-fat,high-sugar di-et).After eight weeks of feeding according to the specified diets,rats in the modeling group were intraperitoneally injected with strepto-zocin(STZ)to establish the model.Then the successfully modeled rats were divided into the model group,the Bifidobacterium group(175 mg·kg-1·d-1),and Dachaihu Decoction low-(8 g·kg-1·d-1),medium-(16 g·kg-1·d-1),and high-dose(32 g·kg-1·d-1)groups,with six rats in each group.Rats in each treatment group were administered the corresponding drugs via gavage,while the normal and model groups received saline via gavage,for eight consecutive weeks.During the intervention period,the modeled rats continued to receive a high-fat diet.After the experiment,levels of fasting plasma glucose(FPG),total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT),and aspartate transferase(AST)were detected using a biochemical analyzer.HE staining was used to observe the pathological changes of liver tissues in each group of rats.Western blot was used to detect the protein expression levels of phosphorylation-phosphatidylinositol 3-kinase(p-PI3K),phosphorylation-protein kinase B(p-PKB,also known as p-AKT),and aquaporin 9(AQP9)in liver tissues.Results:Compared with the normal group,levels of FPG,TC,TG,LDL-C,A LT,and AST were significantly increased,while HDL-C levels were significant-ly decreased,and protein expression levels of p-PI3K,p-AKT,and AQP9 in liver tissues were significantly reduced in the model group.Compared with the model group,levels of FPG,TC,TG,LDL-C,AST,and ALT significantly decreased,while HDL-C levels significantly increased,and protein expression levels of p-PI3K,p-AKT,and AQP9 in liver tissues significantly increased in all treatment groups,and all the differences were statistically significant(P<0.05).HE staining showed that Dachaihu Decoction groups alleviated liver cell damage to varying degrees,with the low-dose Dachaihu Decoction group showing the most significant effect.Conclusion:Dachaihu De-coction can improve glucose and lipid metabolism in the liver by regulating the"gut-liver axis,"thereby bettering liver injury in rats.This effect may be related to its function of regulating the PI3K/AKT/AQP9 signaling pathway.