Effect and mechanism of miRNA-92a regulating SHH pathway on promoting vascular regeneration after myocardial I/R injury
10.3969/j.issn.1009-0126.2023.10.018
- VernacularTitle:微小RNA-92a调控音猥因子途径对心肌缺血再灌注损伤后促血管再生的影响及机制
- Author:
Baohua ZHU
1
;
Yanjun SUN
;
Min LI
Author Information
1. 271199 济南市人民医院全科医学科
- Keywords:
hedgehog proteins;
myocardial reperfusion injury;
circulating microRNA;
cell hypoxia;
apoptosis;
miR-92a
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2023;25(10):1083-1087
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect and mechanism of miR-92a regulating sonic hedgehog(SHH)pathway on promoting vascular regeneration after myocardial ischemia-reperfusion(I/R)injury.Methods Primary cardiomyocytes were isolated from newborn SD rats(1 to 3 days old),and then cultured to establish a cellular model of hypoxia/reoxygenation injury.The cardiomyo-cytes were divided into cardiomyocyte normoxia group and cardiomyocyte I/R group.After miR-92a mimic and inhibitor were respectively transfected into primary cardiomyocytes to overex-press or lower its expression,the cells were then grouped into control,I/R,miR-92a mimic and in-hibitor groups.CCK-8 assay was used to determine cell viability,flow cytometry was employed to detect cell apoptosis,ELISA and QT-PCR were applied to detect the expression of VEGF,b-FGF and Ang-1,and Western blotting was performed to measure the expression of SHH signaling pathway related proteins.Results The expression level of miR-92a was significantly higher in the cardiomyocytes from the ischemia/reperfusion(I/R)group than the normoxia group(3.89±0.29 vs 1.53±0.19,P<0.01).Statistical differences were observed among the control group,miR-92a inhibitor group,I/R group,and miR-92a mimic group in the protein levels of SHH(0.57±0.13 vs 0.51±0.11 vs 0.24±0.03 vs 0.14±0.02,P<0.01),of Smoothened(SMO,0.53±0.12 vs 0.49± 0.10 vs 0.14±0.04 vs 0.09±0.01,P<0.01),of glioma-associated oncogene homolog 1(Gli-1,0.56±0.14 vs 0.50±0.13 vs 0.15±0.03 vs 0.08±0.01,P<0.01),and of glioma-associated onco-gene homolog 2(Gli-2,0.58±0.11 vs 0.49±0.12 vs 0.18±0.02 vs 0.11±0.03,P<0.01).Conclu-sion MiR-92a is abnormally highly expressed in cardiomyocytes after I/R injury,and inhibition of miR-92a can activate SHH signaling pathway to promote the expression of angiogenesis factors effectively.