中国中西医结合杂志2026,Vol.46Issue(3):302-309,8.DOI:10.7661/j.cjim.20260112.130
通脉养心丸调控动力相关蛋白1介导线粒体动力学减轻心肌细胞损伤
Tongmai Yangxin Pill Attenuates Cardiomyocyte Injury by Regulating Drp1-Mediated Mitochondrial Dynamics
摘要
Abstract
Objective To investigate the mechanism of Tongmai Yangxin Pill(TMYXP)in ameliorating hypoxia/reoxygenation(H/R)-induced cardiomyocyte injury.Methods H9C2 cardiomyocytes were divided into the following groups:negative control(NC,H9C2-NC cells+10%blank serum),H/R(H9C2-NC cells+10%blank serum),H/R+TMYXP(H9C2-NC cells+10%drug-containing serum),H/R+dynamin-related protein1(Drp1)-Sh(Drp1-silenced H9C2 cells+10%blank serum),H/R+Drp1-OE(Drp1-overexpressing H9C2 cells+10%blank serum),and H/R+Drp1-OE+TMYXP(Drp1-overexpressing H9C2 cells+10%drug-containing serum).After 24 h of culture,all groups except NC were subjected to 2 h of hypoxia followed by 12 h of reoxygenation to establish a myocardial ischemia-reperfusion injury model.The expression of cardiac troponin I(cTn-I),creatine kinase isoenzyme MB(CK-MB),and lactate dehydrogenase(LDH)was measured by ELISA and colorimetric assays.Apoptosis rate,mitochondrial membrane potential,and mitochondrial permeability transition pore(mPTP)opening were detected by flow cytometry.Mitochondrial morphology was observed using fluorescent probes.Western Blot and RT-PCR were performed to assess the expression of apoptosis-related and mitochondrial dynamics-related proteins and mRNAs.Results In the H/R group,mitochondrial network was severely fragmented,fluorescence signals appeared as discrete dots or short rods,and partial mitochondria exhibited blurred cristae and swollen outer membranes.These alterations were ameliorated in the H/R+TMYXP and H/R+Drp1-Sh groups.The H/R+Drp1-OE group showed aggravated ultrastructural damage with vacuolization,which was improved in the H/R+Drp1 OE+TMYXP group.Compared with the NC group,the H/R group exhibited increased overall and early apoptosis rates,elevated expression of cTnI,CK-MB,LDH,mPTP opening,Cleaved Caspase3,Cleaved Caspase9,B-cell lymphoma-2 associated X(Bax),Drp1,pDrp1616,mitochondrial fission protein 1(Fis1),mitochondrial fission factor(Mff)proteins,and cytochrome C(Cyt-C),apoptotic protease-activating factor 1(Apaf-1),Drp1,Fis1,Mff mRNAs,while mitochondrial membrane potential and the expression of B-cell lymphoma-2(Bcl-2),pDrp1637,optic atrophy 1(OPA1)proteins and OPA1 mRNA were decreased(P<0.05,P<0.01).Compared with the H/R group,the H/R+TMYXP and H/R+Drp1Sh groups showed varying degrees of improvement in the above indicators,whereas the H/R+Drp1-OE group showed aggravated injury(P<0.05,P<0.01).Compared with the H/R+Drp1-OE group,the H/R+Drp1-OE+TMYXP group demonstrated significant improvement in these indices(P<0.05,P<0.01).Conclusion MYXP may exert cardioprotective effects against H/R injury by inhibiting Drp1-mediated mitochondrial excessive fission,restoring mitochondrial dynamics balance,and suppressing the mitochondrial apoptotic pathway.关键词
通脉养心丸/动力相关蛋白1/线粒体动力学/缺氧/复氧/细胞凋亡/心肌细胞Key words
Tongmai Yangxin Pill/dynamin-related protein1/mitochondrial dynamics/hypoxia/reoxygenation/apoptosis/cardiomyocyte引用本文复制引用
于瑞,王永霞,王建茹,董政委,高原,朱明军..通脉养心丸调控动力相关蛋白1介导线粒体动力学减轻心肌细胞损伤[J].中国中西医结合杂志,2026,46(3):302-309,8.基金项目
国家科技重大专项(No.2024ZD0522000) (No.2024ZD0522000)
国家自然科学基金项目(No.82074229) (No.82074229)
河南省科技攻关项目(No.212102311079,No.252102310470) (No.212102311079,No.252102310470)
河南省中医药科研专项(No.2024ZY3027) (No.2024ZY3027)
河南省青年人才托举项目(No.2024HYTP043) (No.2024HYTP043)