世界中医药2025,Vol.20Issue(15):2642-2648,7.DOI:10.3969/j.issn.1673-7202.2025.15.007
四逆汤对脓毒症心肌病大鼠心肌内质网应激-自噬的影响
Sini Decoction Modulates Endoplasmic Reticulum Stress and Autophagy in Septic Cardiomyopathy Rats
摘要
Abstract
Objective:To investigate the mechanism by which Sini Decoction(SND)protects against septic cardiomyopathy(SCM)in rats via the endoplasmic reticulum stress(ERS)-autophagy pathway.Methods:A SCM model in Sprague-Dawley(SD)rats was established using cecal ligation and puncture(CLP).A total of 160 female SD rats were randomly assigned to the blank control group,model control group(CLP),SND treatment group(CLP+SND),inducer group(CLP+SND+tunicamycin),and inhibitor group(CLP+SND+4-phenylbutyric acid)according to a random number table,with 32 rats per group.After successful model in-duction and intervention,blood was collected via the abdominal aorta,and serum levels of myocardial injury markers N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin I(cTnI),and heart-type fatty acid-binding protein(FABP3)were meas-ured using ELISA.Heart tissues were subjected to hematoxylin-eosin(HE)staining and Western blot analysis to detect expression of glucose-regulated protein 78(GRP78),protein kinase R-like ER kinase(PERK),phosphorylated PERK(p-PERK),activating transcription factor 4(ATF4),microtubule-associated protein 1 light chain 3A/B(LC3A/B),tumor necrosis factor-α(TNF-α),and nuclear factor-κB p65(NF-κB p65).Results:Compared with the model control group,the SND group showed markedly reduced myocardial edema and necrosis,and serum NT-proBNP,cTnI,and FABP3 levels were significantly decreased(P<0.05).At 18 h,expression of ERS markers GRP78,PERK,p-PERK,and ATF4 was significantly reduced in the SND and inhibitor groups(P<0.05),while inflammatory mediators TNF-α and NF-κB p65 were lower than in the model and inducer groups(P<0.05).Autoph-agy marker LC3A/B expression was significantly increased at 18 h and 24 h,with statistical significance observed at 18 h(P<0.05).Conclusion:SND effectively inhibits overactivation of the ERS-mediated PERK/ATF4 signaling pathway,regulates autoph-agy activity,and exerts cardioprotective effects in SCM rats.关键词
四逆汤/脓毒症心肌病/心肌保护/蛋白激酶R样内质网激酶/转录激活因子4/内质网应激/微管相关蛋白1轻链3A/B/自噬Key words
Sini Decoction/Septic cardiomyopathy/Myocardial protection/Protein kinase R-like endoplasmic reticulum kinase/Activating transcription factor 4/Endoplasmic reticulum stress/Microtubule-associated protein 1 light chain 3A/B/Autophagy分类
医药卫生引用本文复制引用
张茜,李若冰,刘厚颖,代卓青,江四华,陈堆明,秦娟,骆衡,宋国林..四逆汤对脓毒症心肌病大鼠心肌内质网应激-自噬的影响[J].世界中医药,2025,20(15):2642-2648,7.基金项目
国家自然科学基金项目(82460838) (82460838)
贵州省高层次创新型人才("千"层次人才)[黔委人领办发2023-3号] ("千"层次人才)
贵州省"百"层次创新型人才培养项目(黔科合平台人才-GCC[2022]034-1) (黔科合平台人才-GCC[2022]034-1)
贵州省科技计划项目(黔科合支撑-ZK[2024]一般415号) (黔科合支撑-ZK[2024]一般415号)