期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 315, 期 3, 页码 C380-C388出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00310.2017
关键词
Akt; cell apoptosis; LDH; MAPK3; microRNA-1; myocardial infarction; myocardial ischemia-reperfusion injury; PI3K/Akt signaling pathway; sevoflurane
资金
- Key Projects of Shenzhen Municipality Health and Family Planning Commission [SZXJ2017020, SZSM201612056]
Recent studies have uncovered the vital roles played by microRNAs in regulating cardiac injury. Among them, the cardiac enriched microRNA-1 (miR-1) has been extensively studied and proven to be detrimental to cardiac myocytes. Hence, the current study aimed to explore whether miR-1 affects myocardial ischemia-reperfusion injury (MIRI) in rats undergoing sevoflurane preconditioning and the underlying mechanism. After successful model establishment, rats with MIRI were transfected with mimics or inhibitors of miR-1, or siRNA against MAPK3, and then were injected with sevoflurane. A luciferase reporter gene assay was conducted to evaluate the targeting relationship between miR-1 and MAPK3. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were employed to evaluate the expressions of miR-1, MAPK3, phosphatidylinositol 3-kinase (PI3K), and Akt. Additionally, the concentration of lactate dehydrogenase (LDH) was determined. Cell apoptosis and viability were assessed using TUNEL and cell counting kit-8 assays, and the ischemic area at risk and infarct size were detected using Evans blue and triphenyltetrazolium chloride staining. MAPK3 was found to be the target gene of miR-1. miR-1 expressed at a high level whereas MAPK3 expressed at a low level in MIRI rats. Overexpressing miR-1 or silencing MAPK3 blocked the PI3K/Akt pathway to increase cell apoptosis, ischemic area at risk, and infarct area but decreased cell viability and increased LDH concentration. In contrast, miR-1 downregulation abrogated the effects induced by miR-1 mimics or siRNA against MAPK3. These findings indicate that inhibition of miR-1 promotes MAPK3 to protect against MIRI in rats undergoing sevoflurane preconditioning through activation of the PI3K/Akt pathway.
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