The effect and mechanism of retinoic acid-related orphan receptor-α in the resistance of pressure-loaded myocardium injury in mice

Yang Jiachang; Zhang Bin; Zhu Hanzhao; Li Xiayun; Jiang Liqing; Jin Zhenxiao; Liu Jincheng; Duan Weixun; Yu Shiqiang

doi:10.13498/j.cnki.chin.j.ecc.2023.06.11

Abstract：Objective To investigate the protective effects and underlying mechanisms of retinoic acid-related orphan re-ceptor-α(RORα)treatment on myocardial injury induced by pressure overload in adult C57BL/6 mice.Methods The pressure overload induced myocardial injury model was established in mice by 8 weeks after transverse aortic constriction(TAC)surgery.The experimental mice were divided into the following four groups:Sham+null,Sham+RORα,TAC+null,and TAC+RORα groups.The main detection indicators after eight weeks of TAC surgery were as follows:RORα expression levels,cardiac con-tractile function,myocardial fibrosis indicators include the percentage of myocardial perivascular fibrosis,the percentage of myo-cardial interstitial fibrosis,connective tissue growth factor(CTGF)and collagen Ⅰ expression levels;cardiac hypertrophy indica-tors include heart weight/body weight(HW/BW),average cross-sectional area of myocardial cells and expression levels of brain natriuretic peptide(BNP);oxidative stress indicators include reactive oxygen species(ROS)production,malondialdehyde(MDA)levels,superoxide dismutase(SOD)activity,nuclear factor erythroid 2-related factor 2(Nrf2)and superoxide dismutase 2(SOD2)expression levels;inflammatory response indicators include nuclear factors-κ-Gene binding(NF-κB)content and tu-mor necrosis factor-α(TNF-α)expression levels.Results Compared with the TAC+null group,the mice in TAC+RORα group showed significantly higher RORα level with a better cardiac contractile function(P<0.05),lowered the percentage of myocardi-al perivascular fibrosis and myocardial interstitial fibrosis(P<0.05),CTGF and Collagen I expression level(P<0.05),de-creased the heart weight ratio,mean cross-sectional area of cardiomyocytes and BNP expression level(P<0.05),reduced myo-cardial ROS production and MDA content(P<0.05),increased Nrf2 and SOD2 expression levels,declined myocardial NF-κB and TNF-α expression levels(P<0.05).Conclusion Myocardial specific has a protective effect in attenuating pressure overload-ed myocardial injury by inhibiting oxidative stress and inflammatory responses in myocardial tissues,and delaying aortic arch re-duction-induced myocardial hypertrophy and myocardial fibrosis.