强心汤调控p32/OMA1/OPA1通路维持线粒体功能改善慢性心力衰竭小鼠心肌损伤和纤维化  

Qiangxin Decoction regulates p32/OMA1/OPA1 pathway to maintain mitochondrial function and improve myocardial injury and fibrosis in mice with chronic heart failure

作　　者：毛美玲 卢健棋[2] 潘朝锌[2] 朱智德[2] 卢俊燊 卢洁 谢丽钰 陈佳永 肖湘 MAO Meiling;LU Jianqi;PAN Chaoxin;ZHU Zhide;LU Junshen;LU Jie;XIE Liyu;CHEN Jiayong;XIAO Xiang(First School of Clinical Medicine,Guangxi University of Chinese Medicine,Nanning 530000,China;The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China;Guangxi University of Traditional Chinese Medicine Affiliated Traditional Chinese Medicine School,Nanning 530000,China)

机构地区：[1]广西中医药大学第一临床医学院,广西南宁530000 [2]广西中医药大学第一附属医院,广西南宁530023 [3]广西中医药大学附设中医学校,广西南宁530000

出　　处：《药物评价研究》2025年第1期51-59,共9页Drug Evaluation Research

基　　金：国家自然科学基金地区基金(82160887);广西自然科学基金项目(2021GXNSFAA220111);广西岐黄学者培养项目(NO.2022015-003-02);国家中医药传承创新中心项目(2023019-10);广西中医药大学研究生教育创新计划项目(YCBXJ2023024)。

摘　　要：目的探讨强心汤调控p32/OMA1/OPA1通路介导的线粒体功能防治慢性心力衰竭纤维化的作用机制。方法除7只对照组小鼠外,余33只小鼠通过结扎冠状动脉建立慢性心力衰竭小鼠模型,并将存活的28只小鼠随机分为模型组、沙库巴曲缬沙坦(阳性药,15.17 mg·kg^(-1))组及强心汤低、高剂量(21.69、43.38 g·kg^(-1))组,每组7只,对照组、模型组给予等量纯净水,造模后每天ig给药1次,连续4周。进行苏木素-伊红(HE)、Masson染色观察各组小鼠心肌组织病理损伤和纤维化情况;透射电镜观察线粒体损伤情况;免疫组化法和Western blotting法检测心脏组织中补体成分1q结合蛋白(p32)、线粒体内膜蛋白1(OMA1)、视神经萎缩蛋白1(OPA1)的表达情况;生化检测法测定各组小鼠血清中三磷酸腺苷(ATP)含量。结果与对照组比较,模型组小鼠心肌组织损伤严重、心肌纤维化,线粒体碎裂、嵴消失;p32、长链OPA1(L-OPA1)蛋白表达显著降低(P<0.01),OMA1、短链OPA1(S-OPA1)蛋白表达显著升高(P<0.01),血清ATP浓度水平显著降低(P<0.01)。与模型组比较,强心汤高剂量组小鼠心肌组织整齐、纤维化明显改善,p32、L-OPA1蛋白表达显著增加(P<0.01),OMA1、S-OPA1蛋白表达显著降低(P<0.01),血清ATP含量明显增加(P<0.01)。结论强心汤能够积极调控p32/OMA1/OPA1通路发挥维持线粒体供能、减轻慢性心力衰竭模型小鼠心肌损伤和组织纤维化的作用。Objective To investigate the mechanism of effects of Qiangxin Decoction in modulating p32/OMA1/OPA1 pathway-mediated mitochondrial function against fibrosis in heart failure.Methods Except for seven mice in the control group,the remaining 33 mice established a mouse model of chronic heart failure by ligating the coronary artery,and the 28 surviving mice were randomly divided into model group,Qiangxin Decoction low and high dose(21.69 and 43.38 g·kg^(-1))group,and sacubitril valsartan(positive drug,15.17 mg·kg^(-1))group,with seven mice in each group.After modeling,the mice in each group were treated with ig drugs once a day for four consecutive weeks,in control group and model group were given by equal volume of pure water.HE and Masson staining were performed to observe the pathological injury and fibrosis of myocardial tissue in each group.The mitochondrial damage was observed by transmission electron microscope.The expression of p32,OMA1 and OPA1 proteins in cardiac tissues was detected by immunohistochemistry and Western blotting.The content of ATP in serum was determined by biochemical detection.Results Compared with the control group,the model group exhibited severe myocardial damage,fibrosis,mitochondrial fragmentation,and cristae loss,protein expression of p32 and L-OPA1 was reduced(P<0.01),while that of OMA1 and S-OPA1 was elevated(P<0.01),and serum ATP concentration was significantly lower(P<0.01).In comparison to the model group,the myocardial tissue of mice in Qiangxin Decoction high dose groups was well-organized,with significant improvement in fibrosis,protein expression of p32 and L-OPA1 increased(P<0.01),while that of OMA1 and S-OPA1 decreased(P<0.01),and serum ATP levels were significantly elevated(P<0.01).Conclusion Qiangxin Decoction can actively regulate the p32/OMA1/OPA1 pathway,thereby playing a role in maintaining mitochondrial energy supply,and reducing myocardial injury and tissue fibrosis in CHF model mice.

关 键 词：强心汤 慢性心力衰竭 p32/OMA1/OPA1 线粒体 心肌损伤 纤维化 

分 类 号：R285.5[医药卫生—中药学]