MiR-204 reduces apoptosis in rats with myocardial infarction by targeting SIRT1/p53 signaling pathway

摘要

OBJECTIVE: The aim of this study was to investigate the influence of micro ribonucleic acid (miR)-204 on rats with myocardial infarction by targeting the silent information regulator 1 (SIRT1)/p53 signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including: sham-operation group (n=12), model group (n=12) and miR-204 mimics group (n=12). The rats in the sham-operation group only underwent thoracotomy, without myocardial infarction injury. Meanwhile, the rats in model group and miR-204 mimics group were utilized to establish the models of myocardial infarction, and then, intervened with normal saline and miR-204 mimics, respectively. The morphology of myocardial tissues was observed via hematoxylin-eosin (HE) staining. Immunofluorescence was performed to detect the expression of Caspase-3. Target genes of miR-204 were analyzed using bioanalysis software. Western blotting (WB) assay was applied to measure the relative protein expression of SIRT1. MiR-204 expression and the messenger RNA (mRNA) expressions of SIRT1 and p53 were measured via quantitative Polymerase Chain Reaction (qPCR). Furthermore, cell apoptosis was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: HE staining showed that the morphology of myocardial tissues was normal in sham-operation group. Severe myocardial tissue injury was visible in model group, and the injury was relieved in miR-204 mimics group when compared with model group. The results manifested that the positive expression of Caspase-3 in cardiac tissues increased remarkably in the model group and miR-204 mimics group in comparison with sham-operation group (p0.05). Meanwhile, it was evidently lower in miR-204 mimics group than model group (p0.05). Based on the analysis via bioanalysis software, SIRT1 was the target gene of miR-204. WB results revealed that the relative protein expression level of SIRT1 was elevated notably in the other two groups compared with the 2sham-operation group (p0.05). However, it was markedly lowered in miR-204 mimics group in contrast with model group (p0.05). QRT-PCR results demonstrated that the model group and miR-204 mimics group exhibited distinctly lower expression of miR-204 but higher mRNA expressions of SIRT1 and p53 than sham-operation group (p0.05). However, miR-204 mimics group exhibited prominently higher expression of miR-204 but lower mRNA expressions of SIRT1 and p53 than model group (p0.05). Finally, the results of TUNEL assay demonstrated that the apoptosis rate increased remarkably in the model group and miR-204 mimics group when compared with sham-operation group (p0.05). However, it decreased notably in miR-204 mimics group in comparison with model group (p0.05). CONCLUSIONS: MiR-204 reduces the apoptosis level in rats with myocardial infarction via targeted inhibition of the SIRT1/p53 signaling pathway.