Tong Yifan, Huang Xin, Qian Wei, Liu Lijuan
Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwai Zhengjie, Nanchang, Jiangxi Province, 330006, China.
Department of Cardiology, The Third Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China.
J Physiol Biochem. 2025 Jun 5. doi: 10.1007/s13105-025-01098-3.
The incidence of myocardial infarction (MI) has been increasing in recent years, and the cause of acute myocardial infarction is apoptosis due to insufficient coronary myocardial blood supply. PLAC8 is a critical gene in the disease process of MI through GEO database research and analysis of differentially expressed genes (DEGs). In this study, in mice with myocardial infarction caused by surgical ligation of the left anterior descending coronary artery (LAD) and hypoxia-induced H9C2 cells as a model, the myocardium of the model group was found to show severe cardiomyocyte disorders, apoptosis of inflammatory cell infiltration, and ischemic state by HE, TTC, and Tunel staining. The expression of PLAC8 was reduced in the disease model by PCR and Western blot, and the expression of cle-Casp3 and Bax was also found to be high. However, overexpression of PLAC8 in the disease model reversed these processes. MEK/ERK and P65 are the core signaling pathways in the MI model. In this study, we found that the therapeutic effect of PLAC8 was related to the inhibition of the MEK/ERK signaling pathway by overexpression of PLAC8 and antagonism of the MEK/ERK signaling pathway. In conclusion, the inhibition of the MEK/ERK signaling pathway by PLAC8 under hypoxic conditions reduces apoptosis in H9c2 cells, which may provide new ideas for the determination and treatment of MI.
近年来，心肌梗死（MI）的发病率一直在上升，急性心肌梗死的病因是冠状动脉心肌供血不足导致的细胞凋亡。通过基因表达综合数据库（GEO）研究和差异表达基因（DEG）分析，PLAC8是心肌梗死疾病过程中的关键基因。在本研究中，以通过手术结扎左冠状动脉前降支（LAD）诱导心肌梗死的小鼠和缺氧诱导的H9C2细胞为模型，通过苏木精-伊红（HE）染色、氯化三苯基四氮唑（TTC）染色和脱氧核糖核苷酸末端转移酶介导的缺口末端标记（Tunel）染色发现，模型组心肌出现严重的心肌细胞紊乱、炎性细胞浸润凋亡和缺血状态。通过聚合酶链反应（PCR）和蛋白质免疫印迹法（Western blot）检测发现，疾病模型中PLAC8表达降低，同时也发现剪切型半胱天冬酶-3（cle-Casp3）和凋亡相关蛋白（Bax）表达升高。然而，在疾病模型中过表达PLAC8可逆转这些过程。丝裂原活化蛋白激酶/细胞外信号调节激酶（MEK/ERK）和核转录因子-κB（P65）是心肌梗死模型中的核心信号通路。在本研究中，我们发现PLAC8的治疗作用与过表达PLAC8抑制MEK/ERK信号通路以及拮抗MEK/ERK信号通路有关。总之，缺氧条件下PLAC8抑制MEK/ERK信号通路可减少H9c2细胞凋亡，这可能为心肌梗死的诊断和治疗提供新思路。
