通脉养心丸通过激活ERK信号通路增强线粒体功能减轻大鼠心肌缺血再灌注损伤OA
Tongmai Yangxin pills alleviate myocardial ischemia-reperfusion injury by enhancing mitochondrial function via activating the ERK signaling pathway
目的 通过动物和细胞实验揭示通脉养心丸(TMYX)改善MIRI的作用及机制.方法 在SD大鼠中建立MIRI模型,通过心脏超声心动图、心肌梗死面积、心肌病理、心肌酶及血清炎性细胞因子水平评估TMYX改善心肌损伤的作用.采用H9c2细胞建立体外缺氧/复氧(H/R)损伤模型.通过检测细胞活力、凋亡率、活性氧水平、细胞质和线粒体Ca²+浓度、线粒体膜电位、线粒体通透性转换孔(mPTP)开放状态及线粒体呼吸功能来评估TMYX对H9c2细胞的保护作用及其对线粒体功能的影响.最后,用ERK抑制剂和/或TMYX处理体外H/R处理的H9c2细胞,检测线粒体相关指标,以进一步验证TMYX通过调节ERK信号通路改善线粒体功能来减轻H9c2细胞损伤的机制.结果 在体内,TMYX改善了MIRI大鼠的心功能、心肌损伤和心肌病理结构,降低了炎症因子水平、氧化应激水平和心肌梗死面积.在体外,TMYX提高了H/R损伤后H9c2细胞的活力,提高了细胞内ATP和ATP酶水平以及H/R损伤后的线粒体膜电位,降低了细胞凋亡率、ROS水平和mPTP开放程度.当加入ERK抑制剂时,TMYX改善线粒体功能的能力下降.结论 TMYX通过激活ERK信号通路促进线粒体功能来缓解MIRI.
Background To explore the mechanism of Tongmai yangxin pills(TMYX)for improving myocardial ischemia-reperfusion injury(MIRI)in rats.Methods In a SD rat model of MIRI,the therapeutic effects of TMYX were evaluated by cardiac echography,measurement of myocardial infarction area,and examination of myocardial pathology,myocardial enzymes,and serum levels of inflammatory cytokines.In cultured H9c2 cells,the protective effects of aqueous extract of TMYX in the presence or absence of an ERK inhibitor against hypoxia/reoxygenation(H/R)injury and on mitochondrial function were evaluated by assessing cell viability,apoptosis,reactive oxygen species(ROS)levels,cytoplasmic and mitochondrial Ca² ⁺concentrations,mitochondrial membrane potential,mitochondrial permeability transition pore(mPTP)opening,and mitochondrial respiration.The mitochondria-related indicators were measured to validate the role of the ERK signaling pathway in mediating the alleviating effect of TMYX on mitochondrial function in H9c2 cells with H/R injury.Results In rat models of MIRI,TMYX significantly improved cardiac function,alleviated myocardial injury,and reduced inflammatory factor levels,oxidative stress,and myocardial infarction area.In H9c2 cells with H/R injury,TMYX treatment obviously enhanced H9c2 cell viability,increased cellular ATP and ATPase levels and mitochondrial membrane potential,and reduced cell apoptosis rate,ROS level,and mPTP opening.The application of the ERK inhibitor significantly attenuated the protective effect of TMYX on mitochondrial function of H9c2 cells with H/R injury.Conclusion TMYX alleviate MIRI in rats by promoting mitochondrial function via activating the ERK signaling pathway.
王炎炎;宋志会;郭流漓;肖扬;陈瑞;王怡
天津中医药大学中药现代化国家重点实验室,天津 301617||天津中医药大学中医药研究院,天津 301617||天津中医药大学医学技术学院,天津 301617天津中医药大学中药现代化国家重点实验室,天津 301617||天津中医药大学中医药研究院,天津 301617天津中医药大学中药现代化国家重点实验室,天津 301617||天津中医药大学中医药研究院,天津 301617天津中医药大学第二附属医院药学部,天津 300250天津中医药大学中医学院,天津 301617天津中医药大学中药现代化国家重点实验室,天津 301617||天津中医药大学中医药研究院,天津 301617
心肌缺血再灌注损伤通脉养心丸细胞外信号调节激酶线粒体缺氧/复氧H9c2细胞
myocardial ischemia-reperfusion injuryTongmai Yangxin Pillsextracellular signal-regulated kinasemitochondriahypoxia/reoxygenation injuryH9c2 cells
《南方医科大学学报》 2026 (6)
1203-1215,13
Supported by National Natural Science Foundation of China(82474448). 国家自然科学基金(82474448)
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