临床与病理杂志2025，Vol.45Issue(6)：655-663,9.DOI:10.11817/j.issn.2095-6959.2025.250252
亚精胺对心力衰竭糖尿病大鼠心肌细胞PERK和CHOP通路的影响
Effect of spermidine on the PERK and CHOP pathways in myocardial cells of diabetic rats with heart failure
摘要
Abstract
Objective:Endoplasmic reticulum stress(ERS)plays a key role in the pathogenesis of heart failure combined with diabetes.Spermidine has been reported to exert cardioprotective effects by inducing autophagy and alleviating ERS,but it remains unclear whether these effects are mediated via the protein kinase R-like endoplasmic reticulum kinase(PERK)and C/EBP homologous protein(CHOP)signaling pathways to improve myocardial injury in diabetic rats with heart failure.This study aims to investigate the effects of spermidine on the PERK/CHOP signaling pathway in myocardial cells of diabetes mellitus(DM),heart failure(HF),and DM combined with HF(DM-HF)rats. Methods:Thirty-two SD rats were randomly divided into 8 groups(n=4 each):A control group,a HF group,a DM group,a DM+HF group,a control+spermidine group,a HF+spermidine group,a DM+spermidine group,and a DM+HF+spermidine group.Chronic HF rat was induced by abdominal aortic constriction surgery,and type 2 DM was induced by a high-fat diet combined with streptozotocin(35 mg/kg).After model establishment,the first 4 groups received normal drinking water and the latter 4 received spermidine[10 mg/(kg·d)].H9c2 cardiomyocytes were divided into:A cell control(CG)group,a phenylephrine(CP)group,a spermidine(CS)group,a high glucose(HG)group,a high glucose+spermidine(HS)group,a high glucose+phenylephrine(HP)group,and a high glucose+phenylephrine+spermidine(HPS)group.PERK and CHOP levels in myocardial tissues and cardiomyocytes were measured by Western blotting and immunohistochemistry to compare among groups. Results:Compared with the control group,the DM,HF,and DM+HF groups showed significantly increased PERK and CHOP expression in myocardial tissue(all P<0.05).Compared with untreated groups,spermidine administration reduced PERK and CHOP expression in the DM,HF,and DM+HF groups(all P<0.05).In vitro,compared with the CG group,the CP,HG,and HP groups showed increased PERK and CHOP expression in H9c2 cells(all P<0.05).Spermidine treatment reduced PERK and CHOP expression in HG and HP groups(all P<0.05). Conclusion:Spermidine reduces the activity of the PERK and CHOP pathways in myocardial cells of DM rats with HF,suggesting that its cardioprotective effects may be mediated through this pathway.关键词
亚精胺/心力衰竭/糖尿病/蛋白激酶R样内质网激酶/C/EBP同源蛋白Key words
spermidine/heart failure/diabetes mellitus/protein kinase R-like endoplasmic reticulum kinase/C/EBP homologous protein引用本文复制引用
李顺,陈福艳,刘超,郭志琴,陈平安..亚精胺对心力衰竭糖尿病大鼠心肌细胞PERK和CHOP通路的影响[J].临床与病理杂志,2025,45(6):655-663,9.基金项目
广东省自然科学基金(2020A1515010384).This work was supported by the Natural Science Foundation of Guangdong Province,China(2020A1515010384). （2020A1515010384）
