Abstract
Objective To study the protective effect of trimetazidine on myocardial cells in rats with myocardial infarction and explore its effect on ERK signaling pathway. Methods 40 SD rats were randomly divided into the sham operation group, model group, low-dose group, and high-dose group (intra-abdominal injection of trimetazidine 5 mg/kg and 10 mg/kg, respectively), construction of rat myocardial infarction model by coronary artery left anterior descending artery ligation. 7 days after surgery, the survival rate and cardiac function of each group of rats were recorded. The myocardial infarct size was detected by TTC staining. The apoptosis level of rat cardiomyocytes was detected by TUNEL staining. The content of ROS in rat cardiomyocytes was detected by DCFH-DA. Western-blot was used to detection of Caspase-3, Bcl-2/Bax, and ERK signaling pathway-related proteins in myocardial tissue. Results Compared with the model group, the survival rate of the rats in the low-dose group and the high-dose group was significantly increased (P < 0.01), the cardiac function was significantly improved (P < 0.01), the myocardial infarct size was significantly decreased (P < 0.01), the level of apoptosis was significantly decreased (P < 0.01), the content of ROS in cardiomyocytes was significantly decreased (P < 0.01), the protein expression of Caspase-3 and NF-κB in cardiomyocytes was significantly decreased (P < 0.01), and the expression of Bcl-2/Bax and p-ERK were significantly increased (P < 0.01). Conclusion Trimetazidine can activate ERK signaling pathway in cardiomyocytes of rats with myocardial infarction, increase the expression of p-ERK, decrease the content of ROS in cardiomyocytes, decrease the expression of apoptotic proteins, reduce myocardial infarct size, improve cardiac function, and increase myocardial function.
Highlights
The pathogenesis of myocardial infarction (MI) is the damage or death of myocardial cells due to acute ischemia and hypoxia in coronary artery, and the patients often suffer from severe substernal or precordial crushing pain, exacerbated angina, and arrhythmia
Ischemia and hypoxia lead to a massive release of oxygen free radicals in myocardial cells, activate leukocytes to secrete a large number of inflammatory factors, produce apoptosis-related proteins, and damage cell membranes and mitochondrial membranes, damaging myocardial cells [11]
The rat model of MI was established, and it was found that ligating the left anterior descending coronary artery could result in myocardial ischemia and hypoxia, and obvious infarction of myocardial tissues, and significantly weaken the cardiac function of rats
Summary
The pathogenesis of myocardial infarction (MI) is the damage or death of myocardial cells due to acute ischemia and hypoxia in coronary artery, and the patients often suffer from severe substernal or precordial crushing pain, exacerbated angina, and arrhythmia. The prompt surgical intervention and thrombolytic drugs can restore cardiac blood supply, inhibit ischemic myocardial cell death and ventricular remodeling, and significantly improve cardiac function [4]. There is research evidence that trimetazidine can reduce vascular resistance, increase coronary blood flow, obviously improve clinical symptoms of patients with coronary heart disease, and ameliorate the prognosis of MI patients [6]. Zhao et al [7] found that trimetazidine postconditioning has a protective effect on myocardial cells after myocardial ischemia-reperfusion injury. According to the study of Liu et al [9], activating the ERK signaling pathway can suppress the activation of downstream ELK and nuclear factor-κB (NF-κB), exerting an important protective effect against myocardial injury. There are few studies on the effects of trimetazidine on the ERK signaling pathway and myocardial apoptosis in MI. The rat model of MI was established, the protective effect of trimetazidine on myocardial cells in MI rats was studied, and its possible mechanism of action was further clarified
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