MiR-140 protects against myocardial ischemia-reperfusion injury by regulating NF-κB pathway

L.-Y. Hao, Y. Lu, Y.-C. Ma, R.-P. Wei, Y.-P. Jia

Department of Cardiology, Shanxi Yuncheng Central Hospital, Yuncheng, China. luyansxmu@163.com

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• Cardiology

OBJECTIVE: The aim of this study was to investigate the effect of micro ribonucleic acid (miR)-140 on rats with myocardial ischemia-reperfusion injury (MIRI) through regulating the nuclear factor-κB (NF-κB) pathway.

MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into three groups, including sham group (n=12), model group (n=12) and miR-140 mimics group (n=12). In sham group, only thoracotomy was performed without ischemia-reperfusion. In model group, the MIRI model was first established, followed by intervention using normal saline. In miR-140 mimics group, the MIRI model was first established as well, followed by intervention using miR-140 mimics. The content of serum creatine kinase (CK) and lactate dehydrogenase (LDH) was detected, and the morphology of myocardial tissues was observed via hematoxylin-eosin (HE) staining. Meanwhile, the relative protein expression of NF-κB was determined using Western blotting. Quantitative polymerase chain reaction (qPCR) was conducted to evaluate the expression of miR-140. The content of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) was determined via enzyme-linked immunosorbent assay (ELISA). Furthermore, cell apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.

RESULTS: The content of serum CK and LDH rose significantly in model group and miR-140 mimics group when compared with sham group (p<0.05). However, it declined significantly in miR-140 mimics group compared with model group (p<0.05). HE staining results showed that there were no obvious abnormalities in the morphology of myocardial tissues in sham group. However, there were injury and inflammatory infiltration in myocardial tissues in model group. Meanwhile, the structure and morphology of myocardial tissues were improved in miR-140 mimics group compared with those in model group. Western blotting revealed that the relative protein expression of NF-κB was evidently higher in model group and miR-140 mimics group than sham group (p<0.05). However, it was remarkably lower in miR-140 mimics group than that in model group (p<0.05). QPCR results demonstrated that the relative expression of miR-140 in model group and miR-140 mimics group was obviously lower than sham group (p<0.05). However, a markedly higher expression of miR-140 was observed in miR-140 mimics group than model group (p<0.05). ELISA results indicated that model group and miR-140 mimics group had remarkably higher content of IL-1β and TNF-α than sham group (p<0.05). However, miR-140 mimics group had remarkably lower content of IL-1β and TNF-α than model group (p<0.05). TUNEL assay indicated that the apoptosis rate increased obviously in model group and miR-140 mimics group compared with sham group (p<0.05). However, it declined significantly in miR-140 mimics group compared with model group (p<0.05).

CONCLUSIONS: MiR-140 suppresses inflammation and apoptosis in myocardial tissues of MIRI rats through inhibiting the NF-κB signaling pathway, thereby exerting a cardioprotective effect.

 

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