稳心颗粒通过调控PTEN/Akt/mTOR通路减轻ISO诱导的心脏肥大OA

AIM:This study aimed to investigate the mechanism of Wenxin granules in isoproterenol(ISO)-induced cardiac hypertrophy in mice.METHODS:The mice were randomly divided into a control group,an ISO group,and high-,medium-,and low-dose Wenxin granule groups.ISO was administered subcutaneously at 7.5 mg·kg-1·d-1 for 14 consecutive days to induce myocardial hypertrophy.The high-,medium-,and low-dose Wenxin granule groups re-ceived 0.10 g/kg,0.05 g/kg,and 0.025 g/kg,respectively,by gavage.Cardiac function was evaluated using echocar-diography,while wheat germ agglutinin(WGA)staining and hematoxylin-eosin(HE)staining were performed to assess histopathological changes in myocardial tissue.In vitro,H9c2 cells were pretreated with Wenxin granules(5 mg/mL)for 2 h,followed by ISO(10 µmol)treatment to establish a cellular hypertrophy model.Cell viability was assessed using the MTT assay.The mRNA expression levels of the hypertrophic markers atrial natriuretic peptide(ANP)and brain natriuret-ic peptide(BNP)in mouse heart tissue and cultured cells were measured by RT-qPCR,while the expression of related pro-teins was determined by Western blot.RESULTS:In animal experiments,compared with the control group,the ISO group showed decreased ejection fraction(EF)and fractional shortening(FS)(P<0.01),along with increased left ven-tricular internal diameter at end-diastole(LVIDd),left ventricular internal diameter at end-systole(LVIDs),left ventricu-lar posterior wall thickness at end-diastole(LVPWd),and left ventricular posterior wall thickness at end-systole(LVP-Ws)(P<0.05 or P<0.01).RT-qPCR analysis revealed that the mRNA expression levels of ANP and BNP in myocardial tissue were significantly elevated in the ISO group(P<0.01).Western blot demonstrated reduced PTEN protein expres-sion and significantly increased phosphorylation levels of Akt and mTOR,as indicated by the ratios of phosphorylated to to-tal protein(P<0.01).In the cellular experiments,compared with the control group,the ISO group exhibited reduced cell viability and enlarged cell surface area(P<0.01).RT-qPCR results showed elevated ANP and BNP mRNA expression,while Western blot analysis revealed decreased PTEN expression and increased phosphorylation of Akt and mTOR.Com-pared with the ISO group,treatment with high-dose Wenxin granules reversed these pathological and molecular changes in both animal and cellular models(P<0.05 or P<0.01).Furthermore,treatment with the specific PTEN inhibitor VO-ohpic trihydrate(VO-ohpic)abolished the protective effects of Wenxin granules.CONCLUSION:Wenxin granules significant-ly inhibited ISO-induced pathological changes in cardiac hypertrophy,and this protective effect was achieved through mod-ulation of the PTEN/Akt/mTOR signaling pathway.