MicroRNA-374 Exerts Protective Effects by Inhibiting SP1 Through Activating the PI3K/Akt Pathway in Rat Models of Myocardial Ischemia-Reperfusion After Sevoflurane Preconditioning

• Published in: Cellular physiology and biochemistry Vol. 46; no. 4; pp. 1455 - 1470
• Main Authors: Zhang, Shu-Bo, Liu, Tie-Jun, Pu, Guo-Hua, Li, Bao-Yong, Gao, Xiao-Zeng, Han, Xiao-Liang
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: 3' Untranslated Regions; Animals; Antagomirs - metabolism; Apoptosis; Base Sequence; Biotechnology; Cancer; Cardiac function; Cardiomyocytes; Cell division; Cell growth; Creatine Kinase - blood; Cyclin-dependent kinases; Cytokines; Disease Models, Animal; Down-Regulation - drug effects; G1 Phase Cell Cycle Checkpoints; Glycogen Synthase Kinase 3 beta - metabolism; Heart attacks; Heme Oxygenase-1 - metabolism; Interleukin-6 - metabolism; Ischemia; Ischemic Postconditioning; Kinases; Male; Malondialdehyde - blood; Methyl Ethers - pharmacology; Methyl Ethers - therapeutic use; MicroRNA-374; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Myocardial ischemia-reperfusion; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Nitric Oxide Synthase Type II - metabolism; Ostomy; Phosphatidylinositol 3-Kinases - metabolism; Physiology; PI3K/Akt pathway; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Sprague-Dawley; Retracted Paper; RNA Interference; RNA, Small Interfering - metabolism; Rodents; Sequence Alignment; Sevoflurane; Signal Transduction - drug effects; SP1; Sp1 Transcription Factor - antagonists & inhibitors; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - metabolism; Superoxide Dismutase - blood; Transcription factors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor Suppressor Protein p53 - metabolism; Up-Regulation - drug effects; Beijing China; United States > US; China; Sevoflurane; PI3K/Akt pathway; MicroRNA-374; Myocardial ischemia-reperfusion; SP1
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000489186

Ischemic heart disease is a leading cause of death in cardiovascular diseases, and microRNAs (miRs) have been reported to be potential therapeutic targets in heart disease. Herein, this study aims to investigate the effects of microRNA (miR)-374 on myocardial ischemia-reperfusion (I/R) injury in rat models pretreated with sevoflurane by targeting SP1 through the PI3K/Akt pathway. SD rats were grouped into sham, I/R and sevoflurane + I/R (sevoflurane preconditioning and I/R) groups. The biochemical indicators, pathological changes, positive expression of SP1 protein, and apoptosis rates were measured using biochemical detection, Evans blue-TTC staining, immunohistochemistry and TUNEL staining. RT-qPCR and Western blotting were used to investigate the expression of miR-374 mRNA and the protein expression of SP1, PI3K, HO-1, p53, iNOS, c-fos, Akt/p-Akt, and GSK-3β/p-GSK-3β. Cardiomyocytes were treated with miR-374 mimics, miR-374 inhibitors, or siRNA-SP1. Cardiomyocyte proliferation and cycle distribution and apoptosis were studied by MTT and flow cytometry. Compared with the I/R group, in the sevoflurane + I/R group, serum SOD and IL-10 increased, while MDA, LDH, CK, TNF-α, IL-6 and IL-10 decreased, as did the percentage of infarct area, the positive rate of SP1 and the apoptosis index. The expression of SP1, p53, iNOS and c-fos decreased, and the miR-374 expression of PI3K, HO-1, Akt/p-Akt, GSK-3β/p-GSK-3β increased. With the upregulation of miR-374 and the downregulation of SP1, the expression of SP1, p53, iNOS and c-fos decreased, as did the proportion of cells in G1 phase and the apoptosis rate; the expression of PI3K, HO-1, Akt/p-Akt, GSK-3β/p-GSK-3β increased. The results in the miR-374 inhibitor group contrasted with the above results. The results indicated that miR-374 could alleviate myocardial I/R damage in rat models pretreated with sevoflurane by targeting SP1 by activating the PI3K/Akt pathway.