To Determine The Effects Of Fuzheng Huayu (FZHY) Formula In Improving Myocardial Fibrosis Following Sustained Pressure-overload Hypertrophy In Rats

Objective:1. To determine the cardiac structural changes and molecular events involving in Myocardial Remodeling and Fibrosis during sustained pressure-overload hypertrophy in Rats.2. To determine the effects of Fuzheng Huayu (FZHY) capsule in improving myocardial fibrosis and remodeling following sustained pressure-overload hypertrophy in Rats.Method:1. To make sustained pressure-overload cardiac hypertrophy in rats, constriction of suprarenal abdominal aorta was performed in rats in order to make model, then to compare the heart structural changes of eight weeks and four weeks model rats, using echocardiographic techniques, and then parameters involving in myocardial fibrosis including CollagenⅠ, CollagenⅢ, TGF-β1 mRNA gene expression, and TGF-β1 protein of 4 weeks and 8 weeks model rats were evaluated using pathologic techniques, Gene Chip and confirming through Real-time PCR.2. To study the efficacy of Fuzheng huayu (FZHY) capsule in left ventricular remodeling and fibrosis induced by Constriction of abdominal aorta, the rats were divided into four groups including model group, sham-operated group, Captopril group, and Fuzhenghuayu capsule group, then evaluating the parameters involving in myocardial fibrosis including heart structure, CollagenⅠ, CollagenⅢ, TGF-β1 mRNA gene expression, and TGF-β1 protein of 4 weeks and 8 weeks model rats using pathologic techniques, Gene Chip and confirming through Real-time PCR of eight weeks and four weeks rats.Result:1. Compared with sham-operated group, four and eight weeks after operation, cardiac structures including IVSTd, LVPWTd, LADs, LVM, LVMI of the model group were significantly increased, P<0.01; LVDd is significantly decreased, P<0.01; collagen TypeⅠ, collagen typeⅢ, andⅢ/Ⅰratio are significantly increased after four and eight weeks of operation, P<0.01; compared with four weeks model group, IVSTd, LVPWTd, LADs, LVM, LVMI of eight weeks model group were significantly increased, and LVDd had no difference, P>0.05. 2. Compared with model group, IVSTd, LVPWTd in Fuzheng Huayu group became significantly decreased. Fhuzheng huayu can lessen collagen type 1 and 3 deposition on myocardium tissue P<0.01, however Captopril group has the best effect in inhibiting type I, and type III collagen, P<0.013. There was a positive correlation between the left ventricular ejection fraction (EF%) and CollagenⅢ/Ⅰratio:Ejection Fraction (EF= K. CollagenⅢ/Ⅰ4. Compared with the sham group:TGF-β1 protein density and TGF-β1 mRNA Gene Expression, in model group were significantly increased, P value<0.01.5. Compared with model group:in Captopril and FZHY groups, TGF-β1 protein density was significantly reduced, P value<0.016. Compared with model group,4 weeks and 8 weeks after modeling:TGF-β1 mRNA Gene Expression was significantly reduced in FZHY group and Captopril group, P value<0.05.7. Compared with the sham operated group:ROCK-2 Gene Expression in model group, Captopril group and FZHY group was increased, and Compared with model group:ROCK-2 Gene Expression in Captopril group and FZHY groups was reduced, but not significant P value>0.05.8. Based on our GENE CHIP Analysis, ROCK Gene expression had more important role than Smad proteins in creating cardiac fibrosis in TGF-P pathway in pressure-overload myocardial fibrosis.Conclusion:1-Constriction of suprarenal of abdominal aorta can induce characteristics of concentric hypertrophy and Myocardial Fibrosis eight weeks after operation on Rats.2-Fuzheng Huayu can improve concentric hypertrophy or myocardial fibrosis of model rats.3-Fuzheng Huayu can reduce TGF-β1mRNA Gene Expression in myocardial fibrosis in model rats.