| Objective To investigate the effects of astragaloside IV on myocardial CTGF、TGF β 1 of chronic heart failure modle in rats which were induced by abdominal aorta constriction and to study inhibition of astragaloside IV on myocardial fibrosis in rats and improvement of heart function role whether by inhibiting the expression of CTGF and TGF β 1 to play a role.Methods 120 male Sprague-Dawley rats were Purchased.110 of them were carried on by abdominal aorta constriction.The left rats were the same operation except ligation. There were 60 rats alive after abdominal aorta constriction.Then 60 rats were divided randomly into six groups:a (sham), a (model), and astragaloside IV low dose group (20mg/kg), astragaloside IV medium dose group (40mg/kg) and astragaloside IV high dose group (60mg/kg), valsartan group (10mg/kg). There were 12 rats in each group and the rats of sham-operation group were all survived.After 8 weeks, cardiac ultrasound and hemodynamics inspection would be carried on to make sure the succeed of chronic heart failure model. Then gived the corresponding dose of astragaloside IV (astragaloside IV group) and valsartan(valsartan group), saline (the sham-operation group and model group), once per day, total for 4 weeks.After 4 weeks, cardiac ultrasound and hemodynamics inspection would be carried on again.The hearts were taken out and left ventricular myocardium was free,then HW/BW,LVW/BW would be calculated.Myocardial tissue was used for HE staining and Masson staining.The morphology of the myocardial tissue and the degree of myocardial fibrosis were observed by the microscope, Collagen volume fraction(CVF) was calculated by using image processing system.RT-PCR was used to monitor expression level of myocardial tissue CTGFmRNA,and TGF β 1mRNA.Immunohistochemistry staining was performed to measure the expression of connective tissue growth factor (CTGF) and transforming groth factor-β 1 (TGF-β 1) and the related image processing system was used for quantitative analysis. Western-blotting was used to measure the expression of CTGF and TGF-β 1 again. The universal ChemiDocMP imaging analysis system was used for image processing, with integral absorbance ratio as the relative expression of CTGF, TGF-3 1.The SPSS 17.0 for win 7 statistical software was used for statistical analysis, each data was expressed as means±S.D. Only one-way analysis of variance was used to analyze the differences between two groups, P<0.05 was considered statistically significant. Compared with model group, radix astragali a nucleoside group LVEDP, LVSP, IVSd, LVPWd decreased significantly (P< 0.05 or P< 0.01).+dp/dtmax, dp/dtmax, LVEDd rise significantly (P< 0.05 or P< 0.01).Results (1) model group rats were exprssed, slow, suppress asthma obviously and double leg edema after activities.symptoms and signs of the remaining groups is not obvious.(2) Compared with control group, model group rats related indicators of hemodynamic and echocardiographic changes significantly.The left ventricular end-diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP), end-diastolic ventricular septal thickness (IVSd), left ventricular posterior wall thickness (LVPWd) significantly increased (P< 0.01).The increased rate of left ventricular pressure maximum (+dp/dtmax), left ventricular pressure maximum decline rate (-dp/dtmax), left ventricular end-diastolic diameter (LVEDd) decreased significantly (P< 0.01),(3) HE staining and Masson staining,sham operation rat myocardial cells with clear boundary, the same cell size, did not have cell edema, hypertrophy and obvious fibrous tissue stromal cell.Disorder in arrangement of model group rats cell size and cell hypertrophy were obvious.Astragaloside IV group improved significantly, showing obvious dose-dependent,.CVF compared with model group significantly decreased (P< 0.05 or P< 0.05).(4) In RT-PCR.compared with sham operation group, model group CTGF mRNA, TGF β 1 mRNA expression level increased significantly (P< 0.01).Compared with model group, astragaloside IV group CTGF mRNA, TGF β 1 mRNA expression level of differently decreased (P< 0.01 or P< 0.01).(5) In the immunohistochemical and Western-blotting, compared with control group, model group rats myocardial tissue CTGF, TGF β1 expression level increased significantly (P< 0.01).Compared with model group, astragaloside IV group and valsartan group rats myocardial tissue CTGF, TGF β 1 expression level decreased (P< 0.01 or P< 0.05).Conclusion (1) The abdominal aorta constraction in 8 weeks after operation can form the rat model with chronic heart failure, The primary mechanism is to increase the afterload of the heart.(2)Astragaloside IV can improve cardiac function and play a role of inhibition of myocardial fibrosis, the specific mechanism may be related to astragaloside IV inhibition of the expression of CTGF and TGF β 1.(3) Astragaloside IV has the inhibition of CTGF and TGF β 1 in chronic heart failure rat model rendering a dose dependent. |
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