Effects Of Wenyang Zhenyu Granule On P38 Expression And Apoptosis In Rabbit Cardiomyocytes Induced By Adriamycin - Induced Chronic Heart Failure Model Based On P38 Signal Pathway

Objective:By observing the effects of WYZS granule for heart structure and function of rabbit model with CHF, To investigate the effect of SB203580,a p38inhibitor, in animal model, and to assess the effective dose of this compound,.And based on serum NT-proBNP、expression of proteins of P38lightning (T-P38lightning)、P38lightning phosphorylation level of protein expression (P-P38lightning)、P38lightning detection and quantitative analysis of the expression of mRNA transcription level, and myocardial ultrastructure on electron microscopy.Methods:Part One:40rabbits was divided into8groups:untreated group, adriamycin and DMSO-treated group and DMSO group, SB+adriamycin20dose group, SB+adriamycin40dose group, SB blank group, enalaprilat group. After four weeks of treatment, we harvested the heart tissue, and then assess the expression proteins of P38lightning and phosphorylation of P38by using western-blot and P38mRNA of PCR.Part Two:Based on the result of frist part,56rabbits was divided into8groups: untreated group, adriamycin and DMSO-treated group and DMSO group, SB+adriamycin20dose group, SB+adriamycin40dose group, SB blank group, enalaprilat group. The serum NT-proBNP、T-P38、phosphorylation of P38and P38mRNA,and myocardial ultrastructure.Results:Part One:At the end of4th, the level of phosphorylation of P38increased, SB20ul group、SB40ul group and enalaprilat group lower than adriamycin group, SB40adriamycin was lowest of this three group,the T-P38and P38mRNA of experimental groups at the end of4th weeks were not significantly difference (P>0.05),Part Two:1. Comparison of serum NT-proBNP in each groups, the experimental groups were higher than the untreated group、DMSO group、SB blank group at the end of8th weeks(P<0.05),SB inhibitor>、enalaprilat group、the wenyangzhenshuai granule higher than the untreated group (P<0.05), the wenyangzhenshuai granule slower than other two groups (P<0.05).2. Comparison of apoptosis index in each groups, the experimental groups were higher than the control group at the end of8th weeks(P<0.05), DMSO-treated group is highest of these groups,SB inhibitor、enalaprilat group、the wenyangzhenshuai granule the wenyangzhenshuai granule slower than DMSO-treated groups (P<0.05),. the wenyangzhenshuai granule was lower than other two groups (P<0.05)3. The T-P38and P38mRNA of experimental groups at the end of8th weeks were not significantly difference (P>0.05).4. At the end of8th, the level of phosphorylation of P38increased of SB adriamycin group、wenyangzhenshuai granule and enalaprilat group lower than adriamycin group, it had significantly difference (P<0.05),SB40adriamycin was lowest of this three group (P <0.05).5.Results of electron microscopy:In the experimental control group and drag intervention groups, the muscle fiber were necrosis or atrophy, mitochondria edema and vacuolization, filament structure is also not clear and with inflammatory cells infiltration. The myocardial pathological changes in SB adriamycin group、wenyangzhenshuai granule and enalaprilat group were better than the other groups, wenyangzhenshuai granule was best of this three groups.Conclusions:1. Inhibitor used in the body for a long time effective dose for SB40ul group,4weeks continuous subcutaneous injection can significantly reduce the level of P38lightning protein phosphorylation.2. WenYangZhen failure particles can be adjusted by heart failure model of rabbit heart function, reduce the serum NT-proBNP and P38lightning expression levels of total protein and P38lightning phosphoprotein, P38mRNA and improve myocardial cell structure, so as to prevent and delay the further deterioration of CHF, WenYangZhen failure group curative effect is more better than SB inhibitors.