The Effect Of Qiliqiangxin On Attenuating Pathological Cardiac Hypertrophy And The Underlying Mechanism

Objective: Heart failure is a severe cardiovascular disease with high risk and mortality which influences patients’ prognosis and quality of life.Pathological cardiac hypertrophy is a common incidental symptom and clinical manifestation in heart failure which significantly affects its progression.At present,there is still no effective strategy to pathological hypertrophy.Our previous study a multicenter randomized double-blind parallel-group placebo-controlled study demonstrated effects of qiliqiangxin capsules in patients with chronic heart failure.To further investigate the protective effect of qilqiangxin on cardiac diseases,phenylephrine an α-receptor agonist was used to induce cardiac pressure overload,subsequently mice developed develop into pathological cardiac hypertrophy.By this study,we will further reveal the effect of qiliqiangxin on pathological hypertrophy and the underlying molecular mechanism.Materials and methodsAnimal experimentsMale C57BL/6 mice were implanted subcutaneously with Osmotic mini-pumps at the dorsum of the neck to infuse a pressor dose of phenylephrine(40mg.Kg-1.d-1)for 3 weeks.The control mice were treated with the same procedure except their pumps were filled with vehicle.At the same time,the Chinese medicine qiliqiangxin(QLQX)were administrated at a dose of 0.5 g.Kg-1.d-1 for 3 weeks.Three weeks later,echocardiography was performed on mice using a Vevo 2100,the following parameters were performed: EF%,IVS,LVPW.After the examination,the mice heats were isolated and were performed with Hematoxylin-Eosin(HE)staining to evaluate cardiomyocyte hypertrophy.Q-PCR(Quantitative real time PCR)was used to detect the expression of hypertrophic markers ANP and BNP.Western blot was used to examine the molecular pathway.Vitro experimentsThe primary neonatal rat ventricular cardiomyocytes(NRVMs)were isolated and digested.PE(50μM)was used to induce pathological cardiomyocyte hypertrophy.The expression of PPAR γ and PGC-1 α was detected by western blot analysis.Subsequently,qiliqiangxin(0.5μg/ml)was used to treat cardiomyocyte and identify that if qiliqiangxin has a protective effect on pathological cardiomyocyte hypertrophy.Further,the si RNA of PGC-1α、inhibitor or agonist of PPAR γwas respectively used,to examine its role in qiliqiangxin preventing pathological cardiomyocyte hypertrophy.ResultsVivo experiments indicated that IVS and LVPW of mice were significantly increased induced by PE.And the hypertrophic markers of ANP、BNP were both increased in vivo and vitro,while the expression of PPAR γand PGC-1αwere reduced.The experiments further demonstrated qiliqiangxin treatment activated the PPAR γ and PGC-1α,reduced cardiac hypertrophy and protected cardiac function.Later,the cardiomyocyte were transfected with si RNA of PGC-1α、inhibitor or agonist of PPAR γ,which indicated transfection of si RNA of PGC-1αor inhibitor of PPAR γabrogated the protective effect of qiliqiangxin on pathological cardiomyocyte hypertrophy.ConclusionsQiliqiangxin can attenuate PE induced pathological cardiac hypertrophy by activating PPAR γ and its coactivator PGC-1α,which is probable to benefit to heart failure induced by pathological cardiac hypertrophy,provide a new orientation to treatment of heart failure.