Anti-cardiac Hypertrophy Effect Of Sodium Ferulate In Spontaneously Hypertensive Rats And Its Mechanism Study

Objective:To investigate the effect of sodium ferulate?SF?on cardial hypertrophy in spontaneously hypertensive rats?SHR?and explore its possible mechanism.Methods:14-week old male SHR rats were randomly divided into model group?SHR?,SF?20,40 and 80 mg/kg/day?and Lacidipine?0.5 mg/kg/day?.Age-matched male Wistar-Kyoto?WKY?rats were served as normal controls.Blood pressure was monitored weekly in all rats for 12 weeks of continuous administration;left ventricular structure and function were measured by Vevo 2100 high resolution animal ultrasound imaging system;the pathological morphology of left ventricular myocardium was observed by light microscope and ultrastructure of rat cardiomyocytes was observed by electron microscope.As cardiacatrial hypertrophy markers,natriuretic peptide?ANP?and beta-myosin heavy chain??-MHC?were detected;the levels of calcium-sensing receptor?CaSR?,calcineurin?CaN?,nuclear factor of activated T cell 3?NFAT₃?,phosphorylation NFAT₃?p-NFAT₃?,zinc finger transcription factor?GATA₄?,phosphorylation GATA₄?p-GATA₄?,protein kinase C beta?PKC-??,Raf-1,extracellular regulated protein kinase1/2?ERK 1/2?,phosphorylation ERK1/2?p-ERK 1/2?and mitogen-activated protein kinase phosphatase-1?MKP-1?were observed in rat myocardium.Results:The blood pressure of WKY rats was normal during the experimental period,and the blood pressure of model group rats increased with age.Compared with WKY rats,the left ventricular wall thickened,the left ventricular inner diameter decreased and the indicators of cardiac hypertrophy,myocardial cell cross-sectional area increased significantly in model group rats.At the same time,myocardial histology and cellular ultrastructure were obviously damaged.The levels of ANP,?-MHC and CaSR,CaN,NFAT₃,p-GATA₄,PKC-?,Raf-1 and p-ERK 1/2 were significantly up-regulated,and the expression of p-NFAT₃,MKP-1 were significantly down-regulated in model group rats.SF and Lacidipine could reduce blood pressure,improve the left ventricular function significantly,inhibit left ventricular wall thickening,increase left ventricular inner diameter and left ventricular-stroke volume,decrease left myocardial hypertrophy parameters of SHR rats.The myocardial cell cross-sectional area decreaced significantly,myocardial pathological morphology and ultrastructural of cardiomyocytes were obviously ameliorated by SF.Not only that,SF could significantly down-regulate the levels of ANP,?-MHC,CaSR,CaN,NFAT₃,p-GATA₄,PKC-?,Raf-1 and p-ERK 1/2,while up-regulate the levels of p-NFAT₃ and MKP-1.Conclusion:SF can inhibit cardiac hypertrophy in SHR rats,and its mechanism is closely related to inhibition of CaSR mediated CaN-NFAT₃ signal pathway and PKC-MAPK signal pathway.