Protective Effects Of Astragaloside ? On Liver Injury In Diabetic Rats And Its Mechanism

Objective: To investigate the protective effect of Astragaloside ?(AS-?)on liver injury in diabetic rats and its potential mechanism,and to provide theoretical and experimental evidence for astragaloside ? in the treatment of diabetic metabolic liver injury.Methods Diabetic rats model was established by intraperitoneally injecting(ip)of streptozotocin(STZ)60 mg/kg.(STZ with p H 4.2,0.1mmol/L sodium citrate buffer solution,now with the first to ensure that the injection is completed within 30min).After 72 hours,fasting blood glucose(FBG)and FBG ?11.1 mmol/L in the tail vein were determined to be diabetic model rats.(20,40 and 80 mg/kg)and ROG group(1.28 mg/kg)were randomly divided into diabetic model group(DM group),normal control group was given equal volume of carboxymethyltransferase Sodium cellulose solution,each group of 8,once a day,continuous treatment for 6 weeks.The changes of body weight and fasting blood glucose(FBG)in the rats of each group were measured.Blood samples were collected at the end of the last dose,and the radioactivity was measured by radioactivity The level of serum fasting insulin(FISN)was detected by immunoassay.The activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST),Triglyceride(TG),Total cholesterol(TC),high density lipoprotein(HDL)and low density lipoprotein(LDL)in liver tissue were measured by UV-visible spectrophotometer.The GSH-Px,T-SOD and MDA in the liver tissue were observed by HE staining and histopathological changes were observed by HE staining and immunohistochemistry(IHC)were used to detect the expression of insulin receptor substrate 2(IRS-2).phosphatidylinositol 3-kinase(PI3K),phosphorylated protein kinase B(p-AKT)and glucose transporter 4(GLUT-4)were detected by Western blotting(WB).Results1.Compared with the normal group,the mental fatigue and activity of the model group were decreased,and the symptoms of "three more and one less" were obvious.The typical symptoms of diabetes and the general state of the rats in AS-?(20?40?80 mg/kg)group and ROG(1.28 mg/kg)group were improved obviously.2.Compared with model group,the levels of FBG,FISN,HOMA-IR and ISI were significantly increased in AS-?(40,80 mg/kg)group(P<0.01).3.Compared with the normal group,the liver index,serum TG,TC,ALT,AST of the model group increased significantly,but the body weight was significantly reduced(P<0.01).Compared with the model group,The liver index,serum TG,TC,ALT and AST levels were significantly decreased,while the body weight and HDL were significantly increased in the AS-? treatment group(P<0.05).4.T-SOD and GSH-Px in the model group decreased significantly(P<0.01),and the activities of T-SOD and GSH-Px in the AS-?(40?80 mg/kg)group were significantly increased,MDA content was decreased(P<0.05).5.HE staining showed that the structure of liver lobules in the control group was clear,neat,and no obvious changes were observed.The pathological changes of hepatic tissue were obvious in DM rats,the hepatic cell structure was disturbed,the hepatocytes were swollen,degeneration and necrosis.Inflammatory cell infiltration,AS-?(40?80 mg/kg)and ROG(1.28 mg/kg)groups could alleviate the liver pathological changes in rats.6.The expression of IRS-2 protein in the liver tissue of model group significantly decreased.(P<0.01);AS-?(40,80 mg/kg)and ROG(1.28 mg/kg)group significantly increased the expression of IRS-2 protein(P<0.05).The level of PI3 K,p-AKT and GLUT-4 protein expression were significantly up-regulated in AS-?(40,80 mg/kg)and RSG 1.28 mg/kg)groups(P<0.05,P<0.01).Conclusion AS-? can decrease the blood glucose,serum insulin,TG,TC,ALT and AST activity of diabetic rats,but also can regulate glucose and lipid metabolic disorders,improve liver antioxidant capacity,reduce the degree of liver pathological damage and thus play on diabetic rats The mechanism of action may be to increase insulin sensitivity and improve insulin resistance by up-regulating the expression of IRS-2,PI3 K,phosphorylated AKT and GLUT-4 proteins in the PI3K/AKT signaling pathway in the liver.