电针通过激活肠道FXR/FGF15通路改善糖尿病心肌病小鼠脂质代谢的机制研究OA

Objective To investigate the effects of electroacupuncture on the intestinal farnesoid X receptor(FXR)/fibroblast growth factor 15(FGF15)bile acid signaling pathway in mice with diabetic cardiomyopathy(DCM)and to explore the underlying mechanism by which electroacupuncture(EA)improves lipid metabolism.Methods C57BL/6J mice were randomly divided into a control group,model group,EA group,EA plus inhibitor group,and agonist group(n=8 per group).Except for the control group,DCM models were established by streptozotocin injection combined with a high-fat diet.The EA group received stimulation at Zhongwan(CV/12),Guanyuan(CV/4),Zusanli(ST/36),and Neiguan(PC/6)for 10 weeks.The EA plus inhibitor group was additionally administered the FXR inhibitor Z-Guggulsterone,while the agonist group received the FXR agonist GW4046.Body weight,fasting blood glucose(FBG),lipid profiles,and markers of myocardial injury,oxidative stress,and inflammation were measured.Histopathological changes in myocardial and ileal tissues were examined by HE staining.Protein and mRNA expression levels of FXR and FGF15 in ileal tissue were assessed by Western blot(WB)and real-time quantitative PCR.Results Compared with the control group,the model group showed significantly increased FBG,serum TC,TG,and LDL-C levels,decreased HDL-C and body weight,aggravated myocardial and ileal tissue damage,and downregulated FXR and FGF15 expression(P<0.05).Compared with the model group,these abnormalities were significantly improved in the EA and agonist groups,accompanied by alleviated histopathological injury and upregulated FXR and FGF15 expression(P<0.05).The protective effects of EA were markedly attenuated by FXR inhibition.Conclusion EA may alleviate lipid metabolism disorders and myocardial injury in DCM mice by activating the intestinal FXR/FGF15 signaling pathway.