Di'ao Xinxuekang activates IRS-1/PI3K/Akt signal pathway to improve insulin resistance in nonalcoholic fatty hepatitis mice
AIM:To study the effect and mecha-nism of Di'ao Xinxuekang(DXXK)on insulin resis-tance in nonalcoholic steatohepatitis(NASH)mice.METHODS:C57BL/6J mice were randomly divided into normal group and model group.After 16 weeks of high-fat diet,the model group was ran-domly divided into model group and Pioglitazone group(6.0 mg·kg1·d-1),DXXK high,medium,and low(200,60,20 mg·kg1·d-1)dose groups,with 8 animals in each group,and were administered by gavage for 8 consecutive weeks.The body weight,activity,fat mass,fasting blood sugar(FBG),serum insulin(FINS),total cholesterol(TC),triglyceride(TG),aspartic acid transaminase(AST),alanine ami-no transferase(ALT),and the contents of TC and TG in the liver were measured;oral glucose tolerance test(OGTT),intraperitoneal insulin tolerance test(IPITT),calculate insulin resistance index(HOMA-IR),insulin sensitivity index(ISI),area under curve(AUC)of OGTT and IPITT.HE staining was used to observe liver pathology,and Oil Red O staining was used to observe liver lipid accumulation.Western blot was used to detect the related proteins and downstream target SREBP-1c protein in the IRS-1/PI3K/Akt signaling pathway in liver tissue.RESULTS:Compared with the model group,the body weight,fat mass,FBG,FINS,HOMA-IR,ISI,TC,TG,AST,ALT levels,AUC of OGTT and IPITT in DXXK group and pioglitazone group were significantly reduced,sig-nificant increase in activity,liver lipid deposition and liver function abnormalities were significantly improved,hepatocyte steatosis and ballooning were significantly reduced,and liver p-IRS-1/IRS-1,PI3K,p-AKT/AKT protein expression was significant-ly increased,SREBP-1c protein expression was sig-nificant decrease.CONCLUTION:DXXK can improve insulin resistance in NASH mice,and its mechanism of action may be related to the activation of the IRS-1/PI3K/Akt signaling pathway.