Traditional Chinese Medicine Shen-Yuan-Dan (SYD) Improves Hypoxia-Induced Cardiomyocyte Apoptosis in Neonatal Rats by Upregulating miR-24/Bim Pathway.

Fuyong Chu,Wei Liu,Xue Yan,Xingjiang Xiong,Yixuan Li,Mingxue Zhou,Yupei Tan,Hongxu Liu,Hong Chang

doi:10.1155/2022/5804187

Abstract

Background: Acute myocardial infarction (AMI) is the leading cause of malignant arrhythmia, heart failure, and sudden death. However, safe and effective drugs for the treatment of AMI are unavailable to date. The present study aimed to investigate the role of traditional Chinese medicine shen-yuan-dan (SYD) in hypoxia-induced cardiomyocyte apoptosis in neonatal rats. In addition, the study explored the possible mechanism through which SYD could reduce myocardial ischemia apoptosis and regulate the expression of the miR-24/Bim pathway. Methods: Hypoxia-induced neonatal rat cardiomyocytes were used for the experiments. These cardiomyocytes were transfected with an miR-24 mimic and an miR-24 inhibitor and then cocultured with SYD-containing serum. MTT and lactate dehydrogenase (LDH) assays, AnnexinV/PI double staining, flow cytometry, and TUNEL staining were used to determine the cell viability and apoptosis under hypoxic conditions. Furthermore, the expression level of Bim in the hypoxia-induced cardiomyocytes was determined through western blotting and quantitative real-time polymerase chain reaction. Results: After 48 h of hypoxia, LDH and creatine phosphokinase (CPK) activities increased, cell viability decreased, and miR-24 expression upregulated in the cardiomyocytes. SYD alleviated hypoxia-induced cardiomyocyte injury, decreased LDH and CPK activities, increased cell viability, and reduced apoptosis in the neonatal rat cardiomyocytes. Moreover, SYD could upregulate miR-24 expression and downregulate Bim expression. Upregulation of miR-24 expression significantly enhanced the effect of SYD, thereby improving myocardial cell apoptosis. Dual-luciferase reporter assay and western blot analysis confirmed that Bim was a direct target of miR-24. Conclusion: SYD treatment reduces hypoxia-induced myocardial apoptosis by upregulating miR-24 expression. This study provides new insights into the molecular mechanism underlying the therapeutic potential of SYD in promoting the recovery of myocardial function and delaying the incidence of heart failure.

Highlights

Acute myocardial infarction (AMI) corresponds to acute ischemic myocardial necrosis [1]
lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities increased (Figures 1(b) and 1(c)), cell survival rate decreased (Figure 1(d)), and miR-24 expression increased by 35% (Figure 1(e)). ese results indicated that hypoxia induces myocardial cell injury and that miR-24 may play a role in hypoxia-induced myocardial cell injury
For terminally differentiated cardiomyocytes lacking the regenerative capacity, apoptosis of myocardial cells after MI should be decreased for promoting the recovery of cardiac function and delaying the incidence of heart failure after MI. e results of our study demonstrated that after 48 h of hypoxia, the LDH and CPK activities were obviously increased, the cell viability was decreased, and the myocardial cell apoptosis was significantly increased

Summary

Introduction

Acute myocardial infarction (AMI) corresponds to acute ischemic myocardial necrosis [1]. AMI is characterized by acute onset and high mortality It is the leading cause of malignant arrhythmia, Evidence-Based Complementary and Alternative Medicine heart failure, and sudden death. Acute myocardial infarction (AMI) is the leading cause of malignant arrhythmia, heart failure, and sudden death. The study explored the possible mechanism through which SYD could reduce myocardial ischemia apoptosis and regulate the expression of the miR-24/Bim pathway. Results: After 48 h of hypoxia, LDH and creatine phosphokinase (CPK) activities increased, cell viability decreased, and miR-24 expression upregulated in the cardiomyocytes. SYD alleviated hypoxia-induced cardiomyocyte injury, decreased LDH and CPK activities, increased cell viability, and reduced apoptosis in the neonatal rat cardiomyocytes. Upregulation of miR-24 expression significantly enhanced the effect of SYD, thereby improving myocardial cell apoptosis. Conclusion: SYD treatment reduces hypoxia-induced myocardial apoptosis by upregulating miR-24 expression. Conclusion: SYD treatment reduces hypoxia-induced myocardial apoptosis by upregulating miR-24 expression. is study provides new insights into the molecular mechanism underlying the therapeutic potential of SYD in promoting the recovery of myocardial function and delaying the incidence of heart failure

Methods

Results

Discussion

Conclusion