吉林大学学报（医学版）2026，Vol.52Issue(4)：942-952,11.DOI:10.13481/j.1671-587X.20260407
鹿茸多肽通过调控Keap1/Nrf2/HO-1信号通路对糖尿病心肌病小鼠心肌损伤的改善作用
Promotion effect of velvet antler polypeptide on myocardial injury in diabetic cardiomyopathy mice by regulating Keap1/Nrf2/HO-1 signaling pathway
摘要
Abstract
Objective:To investigate the promotion effect of velvet antler polypeptide(VAP)on myocardial injury in the diabetic cardiomyopathy(DCM)mice,and to clarify its mechanism.Methods:The DCM model was established by feeding a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).Fifty successfully modeled C57BL/6J mice were randomly divided into model group,metformin(Met)group(administered 250 mg·kg-1 Met),low dose of VAP group(administered 100 mg·kg-1 VAP),medium dose of VAP group(administered 200 mg·kg-1 VAP),and high dose of VAP group(administered 300 mg·kg-1 VAP),with once daily administration for 4 weeks;another 10 C57BL/6J mice were used as control group(fed a standard diet).The body weights and fasting blood glucose(FBG)levels of the mice in various groups were monitored;cardiac ultrasound was used to detect the cardiac function of the mice;HE staining was used to observe the pathomorphology of myocardium tissue of the mice;Masson staining was used to observe the degree of myocardial fibrosis of the mice;Oil Red O staining was used to observe the lipid distribution in myocardium tissue of the mice;kits were used to detect the activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the level of malondialdehyde(MDA)in myocardium tissue of the mice;immunohistochemistry staining was used to observe the expression of Kelch-like ECH-associated protein 1(Keap1)in myocardium tissue of the mice;immunofluorescence staining was used to observe the expression of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)in myocardium tissue of the mice;Western blotting method was used to detect the expression levels of Keap1,Nrf2,HO-1,and cysteinyl aspartate-specific proteinase 3(Caspase-3)proteins in myocardium tissue of the mice.Results:Compared with control group,the myocardial injury of the mice in model group was severe,with enlarged myocardial cell gaps,increased collagen fibers,and increased lipid distribution;the body weight,left ventricular posterior wall thickness at end-systole(LVPWs),and ejection fraction(EF)of the mice were significantly decreased(P<0.05 or P<0.01);FBG,left ventricular end-diastolic diameter(LVIDd),and end-systolic diameter(LVIDs)were significantly increased(P<0.05 or P<0.01);the activities of SOD,CAT,and GSH-Px in myocardium tissue were significantly decreased(P<0.01),and the MDA level was significantly increased(P<0.01);the expression levels of Nrf2 and HO-1 proteins in myocardium tissue were significantly decreased(P<0.01),while the expression levels of Keap1 and Caspase-3 proteins were significantly increased(P<0.01).Compared with model group,the pathomorphology,myocardial fibrosis,and lipid distribution of myocardium tissue of the mice in Met group,medium dose of VAP group,and high dose of VAP group were improved to varying degrees;the body weight,LVPWs,and EF were significantly increased(P<0.05 or P<0.01);FBG,LVIDd,and LVIDs were significantly decreased(P<0.05 or P<0.01);the activities of SOD,CAT,and GSH-Px in myocardium tissue were significantly increased(P<0.05 or P<0.01),and the MDA level was significantly decreased(P<0.05 or P<0.01);the expression levels of Nrf2 and HO-1 proteins in myocardium tissue were significantly increased(P<0.01),and the expression levels of Keap1 and caspase-3 proteins were significantly decreased(P<0.01).Compared with model group,the body weight of the mice in low dose of VAP group was significantly increased(P<0.05)and FBG was significantly decreased(P<0.05),but there were no significant differences in LVPWs,EF,LVIDd,LVIDs,activities of SOD,CAT,and GSH-Px,level of MDA,expression level of Keap1,Nrf2,HO-1,and Caspase-3 proteins(P>0.05).Conclusion:VAP can improve myocardial injury and cardiac function in the DCM mice in a dose-dependent manner,and its mechanism may be related to regulating the Keap1/Nrf2/HO-1 signaling pathway and reducing oxidative stress and apoptosis.关键词
鹿茸多肽/糖尿病心肌病/心肌损伤/氧化应激/细胞凋亡Key words
Velvet antler polypeptide/Diabetic cardiomyopathy/Myocardial injury/Oxidative stress/Apoptosis分类
医药卫生引用本文复制引用
黄晓巍,郑彭予,李馨,洪传彬,李萌萌,律广富,徐岩,林喆,许佳明..鹿茸多肽通过调控Keap1/Nrf2/HO-1信号通路对糖尿病心肌病小鼠心肌损伤的改善作用[J].吉林大学学报（医学版）,2026,52(4):942-952,11.基金项目
吉林省科技厅科技发展计划项目(YDZJ202501ZYTS711) （YDZJ202501ZYTS711）
吉林省教育厅大学生创新创业训练计划项目(S202410199038) （S202410199038）
