| Objective: To investigate the effects of sodium ferulate(SF)on myocardial hypertrophy of rat and explore the protective mechanism.Methods: The rat left ventricular hypertrophy was induced by abdominal aorta coarctation.The rats were randomly divided into sham,model and SF(20,40,80mg/kg/d)group.The cardiac function of rats was assessed after the day after surgery for 21 consecutive days.The left ventricular hypertrophy induced by abdominal aorta coarctation was evidenced by histopathology,electromicroscopy,and by determining the elevated left ventricular weight and the expression of aterial natriuretic peptide(ANF)and myosin heavy chain ?(?-MHC).To examine the mechanism of protection,the contents of Ang II and ET-1 in rat myocardial tissue were determined by radioimmunoassay,the expressions of PKC-?,Raf-1,ERK1/2 and MKP-1 were analysised by Real Time PCR and Western blotting.In vitro,the myocardial hypertrophy was induced by 0.1 ?mol·L-1 Ang II.The cytoactive was detected by MTT.The cultured cardiomyocytes from Sprague Dawley neonate rats were randomly divided into normal,model,L-arginine(L-arg 1000 ?mol·L-1)group and SF(50,100,200 ?mol·L-1)group.To observe whether SF had nonspecific injurious effect on the cells,SF 200 ?mol·L-1 was added into the normal cardiomyocytes and to determine whether the effect of SF on cardiomyocyte hypertrophy is associated with NO release,another two groups were established.NG-nitro-L-arginine-methyl ester(L-NAME)1500 ?mol·L-1 combined with SF 200 ?mol·L-1 or L-arg1000 ?mol·L-1,respectively.Cardiomyocyte hypertrophy was confirmed by observing the histological changes and the measurements of cell diameter,protein content and ANF and ?-MHC mRNA expression of the cells.The levels of NO,NOS and eNOS activity,the contents of cGMP and cAMP.The expression of PKC-?,Raf-1,ERK1/2,MKP-1 and eNOS were detected by Real time PCR and Western blotting.Results:(1)Compared with the sham group,left ventricular hypertrophy index(LVHI)and MD in model group were significantly increased,and the blood pressure(BP),left ventricular pressure(LVSP),the cardiac systolic and diastolic activity of LVEDP and ±dp/dtmax were significantly abnormal in indicators.the rat myocardial histopathology was obviously impaired in model group,the expressions of ANF and?-MHC mRNA were up-regulated.Compared with the model group,SF treatment could reduce the index of LVHI and MD induced by AAC surgery,the expressions of ANF and ?-MHC mRNA were also reduced,the rat myocardial histopathology and left ventricular systolic and diastolic function were ameliorated.(2)In model group,the contents of Ang II and ET-1 in myocardial tissue were raised,the expression of PKC-?,Raf-1 and ERK1/2 mRNA and protein were up-regulated and MKP-1 mRNA and protein expression was decreased.SF treatment could attenuate the contents of Ang II and ET-1,decreased the expression of PKC-?,Raf-1,ERK1/2 and increased the expression of MKP-1m RNA and protein level in the myocardium.(3)SF(50,100,200 ?mol·L-1)had no obvious side effect on cultured neonatal rat cardiomyocytes in vitro.In the group added 0.1 ?mol·L-1 Ang II alone,the cells displayed swollen,with undistinguishable border;the diameter and protein content of cardiomyocytes was increased remarkably,and the expression of ANF and ?-MHC mRNA were up-regulated by Ang II.SF and L-arg could ameliorate the cardiomyocyte hypertrophy which can be inhibit by L-NAME.(4)Compared with normal group,0.1?mol · L-1 Ang II could decrease the NO content,NOS and eNOS activity in supernatant of cultured cardiomyocytes,decrease the content of cGMP and increase thecontent of cAMP incardiomyocytes,up-regulation the expression of PKC-?,Raf-1,ERK1/2 and down-regulation the expression of MKP-1 and eNOS.SF-H and L-arg administrated could siginificantly ameliorate these changes.Conclusion: SF can inhibit cardiomyocyte hypertrophy induced by AAC surgery and Ang II in rats.The probable mechanism involved to promote NO/cGMP signaling pathway and inhibit PKC and MAPK signaling pathway. |
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