中国免疫学杂志2025，Vol.41Issue(6)：1376-1382,7.DOI:10.3969/j.issn.1000-484X.2025.06.020
米诺环素调节AMPK/SIRT1/PGC-1α信号通路对糖尿病心肌病大鼠心肌损伤的影响
Impact of minocycline on myocardial injury in diabetes cardiomyopathy rats by regulating AMPK/SIRT1/PGC-1α signal pathway
摘要
Abstract
Objective:To investigate the impact of minocycline on myocardial injury in diabetes cardiomyopathy(DCM)rats by regulating 5'-AMP activated protein kinase(AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator activator receptor gamma coactiva-tor 1α(PGC-1α)signal pathway.Methods:SD rats were fed with high-fat diet for 4 weeks,and then a single intraperitoneal injection of 35 mg/kg streptozotocin was used to induce the DCM model.They were randomly grouped into model group,low-dose minocycline(20 mg/kg)group,high-dose minocycline(40 mg/kg)group,high-dose minocycline+Dorsomorphin(AMPK inhibitor,0.2 mg/kg)group,with 12 rats in each group,another 12 normal rats were fed with normal feed for 4 weeks,and then were given a single intraper-itoneal injection of the same dose of citric acid buffer,which was set as a sham operation group,after the intervention with minocy-cline and Dorsomorphin,and the fasting blood glucose(FBG),total cholesterol(TC)and triglyceride(TG)were measured;left ven-tricular ejection fraction(LVEF)and left ventricular short axis shortening(FS)were measured by ultrasound;HE staining and Mas-son staining were applied to detect the pathological morphology of myocardial tissue of rats in each group;the levels of serum and myo-cardial tissue inflammation IL-6,IL-18,and myocardial tissue oxidative stress indicators-superoxide dismutase(SOD)and malondial-dehyde(MDA)were measured with the kit;Western blot was applied to detect the expression of AMPK/SIRT1/PGC-1α pathway pro-tein in myocardial tissue of rats in each group.Results:Compared with the sham operation group,the myocardial tissue in the model group was seriously damaged,the levels of FBG,TC and TG,the cross-sectional area of myocardial cells and the proportion of myocar-dial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tissue,and the level of MDA in myocardial tissue were obviously increased(P<0.05),the levels of LVEF,FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were obviously decreased(P<0.05);compared with the model group,the myocardial tissue damage of rats in the low-dose and high-dose minocycline groups were reduced,the levels of FBG,TC and TG,the cross-sectional area of myocardial cells and the proportion of myocardial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tissue,and the level of MDA in myocardial tissue were decreased(P<0.05),the LVEF,the levels of FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were increased(P<0.05);compared with the low-dose minocycline group,the myocardial tissue damage in the high-dose minocycline group was further reduced,the levels of FBG,TC and TG,the cross-sectional area of myocardial cells and the proportion of myocardial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tissue,and the level of MDA in myo-cardial tissue were further decreased(P<0.05),the levels of LVEF,FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were further increased(P<0.05);compared with the high-dose minocycline group,the myocar-dial tissue damage of rats in the high-dose minocycline+Dorsomorphin group increased,the levels of FBG,TC and TG,the cross-sec-tional area of myocardial cells and the proportion of myocardial fiber area,the levels of IL-6 and IL-18 in serum and myocardial tis-sue,and the level of MDA in myocardial tissue were increased(P<0.05),the LVEF,the levels of FS and SOD in myocardial tissue,and the protein expression of p-AMPK/AMPK,SIRT1 and PGC-1α were decreased(P<0.05).Conclusion:Minocycline can reduce oxidative stress and inflammation in DCM rats by activating AMPK/SIRT1/PGC-1α signal,and improve glycolipid metabolism,thereby reducing myocardial injury and repairing cardiac function in rats.关键词
米诺环素/AMPK/SIRT1/PGC-1α/糖尿病心肌病/心肌损伤Key words
Minocycline/AMPK/SIRT1/PGC-1α/Diabetes cardiomyopathy/Myocardial damage分类
医药卫生引用本文复制引用
戴婧,郑丽,王亚兰,杨小师,唐凤,黎艳..米诺环素调节AMPK/SIRT1/PGC-1α信号通路对糖尿病心肌病大鼠心肌损伤的影响[J].中国免疫学杂志,2025,41(6):1376-1382,7.基金项目
武汉市医学科研项目(WX21Q23). （WX21Q23）
