Effect of transient receptor potential channel 5 on myocardial injury induced by intermittent hypoxia
Objective:To investigate the underlying mechanism and effects of transient receptor potential channel 5(TRPC5)on myocardial damage in rats exposed to intermittent hypoxia.Methods:A total of twelve TRPC5-/-and twelve SD mice were ran-domized to be placed in the chronic intermittent hypoxia(CIH)group and the control group.Echocardiography was utilized to ob-serve structural and functional changes in the rat hearts.To determine the volume fraction of cardiac collagen,masson staining was used.TUNEL labeling was employed to evaluate the apoptosis of cardiac cells.Flow cytometry was employed to measure ROS and Ca2+concentrations in cardiac tissues.Furthermore,Western blot analysis was used to assess the expression levels of TRPC5,Bcl-2,Bax,Caspase-3,CaN,NFAT2,p-NFAT2,NFAT3,p-NFAT4,and p-NFAT4 proteins in the heart tissues.Results:The left ventricular ejection fraction and fractional shortening were higher in the TRPC5-/--CIH group compared to the CIH group,but lower than in the TRPC5-/--Control group,as evidenced by the cardiac color Doppler ultrasound findings.Additionally,the left ven-tricular volume and internal diameter were lower in the CIH group but higher in the TRPC5-/--Control group(P<0.05).Histologi-cal analysis using HE staining showed that the extent of myocardial fiber disarray in the TRPC5-/--CIH group was more prominent compared to the TRPC5-/--Control group,but less severe than in the CIH group.According to Masson staining,the collagen vol-ume fraction was lower in the TRPC5-/--CIH group compared to the CIH group,but higher than the TRPC5-/--Control group.Rat heart tissue stained with TUNEL revealed that the cardiomyocyte apoptotic rate in the TRPC5-/--CIH group was greater than that in the TRPC5-/--Control group,but it was lower than that in the CIH group(P<0.05).The TRPC5-/--CIH group had higher levels of ROS and Ca2+than the TRPC5-/--Control group,but lower levels than the CIH group,according to the flow cytometry results(P<0.05).Furthermore,Caspase-3,Bax,and CaN expression levels were higher in the TRPC5-/--CIH group compared to the TRPC5-/--Control group,but lower than in the CIH group,according to Western blotting study.In contrast,Bcl-2,p-NFAT2,p-NFAT3,and p-NFAT4 had greater relative expression levels in the TRPC5-/--CIH group than in the CIH group,but lower lev-els in the TRPC5-/--CIH group.(P<0.05).Conclusion:By koncking out the TRPC5 gene,myocardial damage induced by inter-mittent hypoxia may be lessened,oxidative stress and calcium overload may be limited,and the CaN/NFAT pathway may play a role in this mechanism.
国家科技期刊平台
NSTL
万方数据
