Guo Zitong, Qian Geng, Pan Xietian, Zou Yuting, Chen Si, Zhu Qinglei, Chen Zhengju
Department of Cardiology, People's Hospital of Xinjiang Uygur Autonomous Region, China.
Department of Cardiology, Chinese PLA General Hospital, the Sixth Medical Center, Beijing, China.
Int J Med Sci. 2025 Jan 1;22(1):44-52. doi: 10.7150/ijms.102763. eCollection 2025.
Myocardial injury is prone to occur during myocardial ischemia-reperfusion, which further causes adverse cardiac events. Cardiomyopeptide (CMP) has been found to protect the heart against ischemia-reperfusion injury. The present study will explore the molecular and signaling mechanisms associated with the therapeutic effects of CMP. In this study, the rat myocardial ischemia-reperfusion model was constructed, the pathological changes of myocardial tissues were observed via hematoxylin-eosin (H&E) and Masson staining, and the levels of myocardial injury markers (AST, Mb, TnT) were detected by ELISA. Myocardial tissues of rats in each group were analyzed using transcriptome sequencing (RNA-seq), and the obtained gene expression profiles were analyzed differentially to determine differentially expressed genes (DEGs). In addition, the signaling pathway related to CMP therapy was found by gene set enrichment analysis (GSEA), and PPARγ was detected by qRT-PCR, WB, and IHC staining. The mitochondrial function of myocardial tissues was detected by mitochondrial respiratory chain activity, JC-1, and reactive oxygen species (ROS). Animal assays showed that CMP could significantly improve myocardial injury and reduce the levels of AST, MB and cTnT. RNA-seq analysis results showed that PPARγ signaling pathway is a potential signaling pathway for CMP treatment of myocardial injury in rats. The experimental results showed that CMP can significantly up-regulate PPARγ expression in myocardial tissues, inhibit ischemia reperfusion-induced myocardial injury, and alleviate mitochondrial respiratory disorders. CMP can improve myocardial injury in rats by alleviating mitochondrial respiratory dysfunction and reducing myocardial tissue damage and inflammatory infiltration via the regulation of PPARγ signaling pathway.
心肌损伤在心肌缺血再灌注期间容易发生，这会进一步导致不良心脏事件。已发现心肌肽（CMP）可保护心脏免受缺血再灌注损伤。本研究将探索与CMP治疗作用相关的分子和信号机制。在本研究中，构建大鼠心肌缺血再灌注模型，通过苏木精-伊红（H&E）和Masson染色观察心肌组织的病理变化，并采用酶联免疫吸附测定（ELISA）检测心肌损伤标志物（AST、肌红蛋白、肌钙蛋白T）的水平。对每组大鼠的心肌组织进行转录组测序（RNA-seq）分析，对获得的基因表达谱进行差异分析以确定差异表达基因（DEG）。此外，通过基因集富集分析（GSEA）发现与CMP治疗相关的信号通路，并采用实时定量逆转录聚合酶链反应（qRT-PCR）、蛋白质免疫印迹法（WB）和免疫组织化学（IHC）染色检测过氧化物酶体增殖物激活受体γ（PPARγ）。通过线粒体呼吸链活性、JC-1和活性氧（ROS）检测心肌组织的线粒体功能。动物实验表明，CMP可显著改善心肌损伤并降低AST、MB和cTnT水平。RNA-seq分析结果表明，PPARγ信号通路是CMP治疗大鼠心肌损伤的潜在信号通路。实验结果表明，CMP可显著上调心肌组织中PPARγ的表达，抑制缺血再灌注诱导的心肌损伤，并减轻线粒体呼吸紊乱。CMP可通过调节PPARγ信号通路减轻线粒体呼吸功能障碍，减少心肌组织损伤和炎症浸润，从而改善大鼠心肌损伤。
