实用临床医药杂志2025，Vol.29Issue(11)：49-54,60,7.DOI:10.7619/jcmp.20250178
葛根素调控蛋白激酶B/糖原合成酶激酶-3β通路抑制糖尿病心肌病大鼠的心肌细胞铁死亡
Puerarin regulates protein kinase B/glycogen synthase kinase-3β pathway to inhibit ferroptosis of cardiomyocytes in rats with diabetic cardiomyopathy
摘要
Abstract
Objective To investigate the effect of puerarin(Pue)on ferroptosis in myocardial cells of rats with diabetic cardiomyopathy(DCM)and to analyze its potential mechanisms.Methods A DCM rat model was established by high-fat,high-sugar diet combined with streptozotocin injection.The successfully modeled rats were randomly divided into DCM group,low-dose Pue group(125 mg/kg,gavage),high-dose Pue group(250 mg/kg,gavage)and valsartan group(30 mg/kg,gavage),with 10 rats in each group.Another 10 healthy SD rats were selected as blank control group.At the end of treatment,fasting blood glucose,tail artery blood pressure(BP)total cholesterol(TC),triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)levels were measured in all groups.The cardiac function related indicators[left ventricular ejection fraction(LVEF),left ventricular fractional shorten-ing(LVFS),left ventricular end-systolic diameter(LVDs)and left ventricular end-diastolic diameter(LVDd)]of rats in each group were recorded by ultrasonic apparatus.Histopathological changes in myocardial tissues were observed using hematoxylin-eosin(HE)staining and TUNEL staining.Levels of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),reactive oxygen species(ROS),malondialdehyde(MDA)and Fe2+were detected using enzyme-linked immunosorbent as-say(ELISA)kits.Western blotting was used to detect the expression levels of glutathione peroxi-dase 4(GPX4),long-chain acyl-CoA synthetase 4(ACSL4)and proteins involved in the protein kinase B/glycogen synthase kinase-3β(AKT/GSK-3β)signaling pathway.Results Compared with the blank control group,the DCM group exhibited disordered or fractured myocardial fibers and significant inflammatory cell infiltration.The apoptosis rate,LVDs,LVDd,blood glucose,BP,TC,TG,LDL-C,ROS,MDA,Fe2+and ACSL4 protein expression levels in the DCM group were signifi-cantly higher,and LVEF,LVFS,GSH-Px as well as SOD and the protein expression levels of GPX4,phosphorylated(p)-AKT,p-GSK-3β and p-PI3K were lower than those in the blank group(P＜0.05).Compared with the DCM group,the low-dose Pue group,high-dose Pue group and valsartan group showed reduced fractured myocardial fiber or disarray,more regular arrangement of myocardial fibers,and decreased inflammatory cell infiltration.The apoptosis rate,LVDs,LVDd,blood glucose,BP,TC,TG,LDL-C,ROS,MDA,Fe2+and ACSL4 protein expression levels in the low-dose Pue group,high-dose Pue group and valsartan group were significantly lower,and LVEF,LVFS,GSH-Px as well as SOD and the protein expression levels of GPX4,p-Akt,p-GSK-3 βand p-PI3K were significantly higher than those in the DCM group(P＜0.05),and the effect was more significant in the high-dose Pue group.Conclusion Pue treatment can effectively improve the metabolic level of DCM rats,inhibit the pathological damage and apoptosis of cardiomyocytes,alle-viate oxidative stress,and thereby improving the cardiac function of DCM rats.Its mechanism of ac-tion may be related to the inhibition of cardiomyocyte ferroptosis mediated by the AKT/GSK-3βpathway.关键词
葛根素/缬沙坦/蛋白激酶B/糖原合成酶激酶-3β通路/铁死亡/糖尿病心肌病/心肌细胞/心功能/氧化应激Key words
puerarin/valsartan/protein kinase B/glycogen synthase kinase-3β pathway/ferroptosis/diabetic cardiomyopathy/myocardial cells/cardiac function/oxidative stress分类
医药卫生引用本文复制引用
刘超权,郑梅凡,姚亚男..葛根素调控蛋白激酶B/糖原合成酶激酶-3β通路抑制糖尿病心肌病大鼠的心肌细胞铁死亡[J].实用临床医药杂志,2025,29(11):49-54,60,7.基金项目
儋州市科技和工业信息发展局科研项目{儋科工信[2024]77号} （）
