The Protective Effect And Mechanism Of Sanchinone In Pathological Myocardial Hypertrophy

ObjectiveTo investigate the role of Sauchinone in pathologic cardiac hypertrophy and its related regulation pathway.Method1.In vitro experiment H9C2 cardiomyocyte hypertrophy model was induced by isoproterenol.The changes of surface area and total protein content of H9C2 cardiomyocytes in different concentrations of Sauchinone groups(10?mol/L?20?mol/L?30?mol/L)were measured.The expression of cardiac hypertrophy markers Myh7 and Nppa were detected by RT-PCR.The apoptosis of H9C2 cardiomyocytes in different drug treatment groups was detected by flow cytometry.The changes of related pathways were detected by Western-blot.2.In vivo experiment the model of pathological myocardial hypertrophy was established by injecting isoproterenol(ISO)and transverse aortic constrictionation(TAC)in mice.The mice were injected with Sauchinone in the tail vein as the treatment group.After 3 weeks,Heart mass index(cardiac mass index = heart weight/body weight,HW/BW),Left ventricular mass index(left ventricular mass index = left ventricular mass/body weight,LVW/BW),the ratio of Lung weight to body weight(LW/BW),the ratio of tibial length to heart(HW/TL)were measured in different groups of mice.The morphological changes of the cells were observed by HE staining.The expression of Myh7 and Nppa were detected by RT-PCR.Western-blot was used to detect the related pathways.Results1.In vitro experiment The Sauchinone can significantly inhibit isoproterenol induced increasing of myocardial cell surface area and total protein content(P<0.05),The genes of Myh7 and Nppa that expressed in the hypertrophy was decreased,the Isoproterenol induced cardiomyocyte apoptosis rate is reduced and the JNK3 pathway protein was downregulated in the treatment group(P<0.05).2.In vivo experiment The cardiac volume was decreased,the ratio of HW/BW,LVW/BW,LW/BW,HW/TL was significantly decreased and the cardiac hypertrophy marker gene Myh7 and Nppa were down-regulated after treated with Sauchinone in the model of pathological myocardial hypertrophy induced by isoproterenol(P<0.05).The cardiac volume was decreased,the ratio of HW/BW,LVW/BW,LW/BW,HW/TL was significantly decreased and the cardiac hypertrophy marker gene Myh7 and Nppa were down-regulated after TAC model was treated with Sauchinone(P<0.05).The expression of JNK3 pathway protein was down-regulated by the two pathological cardiac hypertrophy models after treated with Sauchinone.Conclusion Sauchinone has protective effect on pathological cardiac hypertrophy,and the protective effect of Sauchinone on pathological hypertrophy may be related to the regulation of JNK3 pathway protein expression.