| Purpose:To explore the effect of astragalus warm heart formula on ventricular remodeling and its molecular mechanism in rats with chronic heart failure(HF).Material and method:Forty SPF SD rats were randomly divided into two groups:blank control group(n=10)and heart failure group(n=30).The HF rats were induced by intraperitoneal injection of adriamycin(Adr)in the heart failure group,and the rats in the blank group were injected with saline of equal volume,six weeks later,Doppler ultrasound diagnostic apparatus was used to detect whether HF rat model was successfully established.27 rats were randomly divided into model control group(model group),captopril control group(captopril group)and Astragalus warm heart formula group(traditional Chinese medicine group).In the captopril group,2.25mg/kg/d captopril was given by gavage;In the traditional Chinese medicine group,9.2g/kg/d Astragalus warm heart formula was given by gavage;In the blank group and model group,normal saline of equal volume was given.Four weeks later,the heart structure and function of rats were detected by Doppler ultrasound;the level of BNP in plasma was detected by ELISA to evaluate the degree of heart failure;the heart tissue morphology was observed by HE staining;the degree of myocardial fibrosis and the collagen volume fraction(CVF)were observed by Masson staining;The related factors MMP-9 and TIMP-1 were detected by RT-q PCR;Western blot was used to detect the expression of RhoA/ROCK signaling pathway protein.Results:1.Cardiac structure and function: Before drug treatment,the ratio of LVIDd in heart failure group and blank group were significantly increased(p<0.05)and LVEF was significantly decreased(p<0.05),which can confirm the successful establishment of HF model in rats after adriamycin injection.After drug treatment,LVIDd was significantly decreased(p<0.05)and LVEF was significantly increased(p<0.05)in the traditional Chinese medicine group and captopril group compared with the model group.There was no significant difference in LVIDd and LVEF between the traditional Chinese medicine group and captopril group(p>0.05).2.Change of plasma BNP: Before drug intervention,the ratio of plasma BNP in heart failure group rats to that in blank group was significantly increased(p<0.05).After drug intervention,plasma BNP in captopril group and traditional Chinese medicine group decreased significantly compared with model group(p<0.05).There was no significant difference between the plasma BNP of rats in the traditional Chinese medicine group and captopril group(p>0.05).3.Myocardial tissue morphology: In the blank group,the myocardium is orderly arranged,the nucleus is intact,and the myocardial cells are free from hypertrophy and atrophy.Interstitial edema,connective tissue hyperplasia and inflammatory infiltration were not found.In the model group,the myocardial cells were arranged in disorder,the fiber thickness of myocardial cells was different,the cell nuclei were different in size,some of the cell nuclei were missing,and fibrous scar foci were visible.The arrangement of myocardial cells in Chinese medicine group and captopril group is relatively neat,myocardial interstitial edema is light,there is a small amount of inflammatory cell infiltration in the interstitium,myocardial fibers have no obvious change,and staining is relatively uniform.4.Myocardial fibrosis: Masson staining showed that myocardial fibrosis in model group was significantly worse than that in blank group,and CVF was significantly increased(p<0.05).Compared with the model group,myocardial fibrosis in captopril group and traditional Chinese medicine group was significantly reduced,and CVF was significantly reduced(p<0.05).There was no significant difference in fibrosis degree and CVF between the Chinese medicine group and captopril group(p>0.05).5.Ventricular remodeling: Compared with the blank group,the expression of MMP-9 m RNA in the model group was significantly increased(p< 0.05),the expression of TIMP-1 m RNA was significantly decreased(p<0.05),and the degree of ventricular remodeling was aggravated.Compared with the model group,the expression of MMP-9 m RNA in myocardium of captopril group and traditional Chinese medicine group decreased significantly(p<0.05),the expression of TIMP-1 m RNA increased significantly(p<0.05),and the degree of ventricular remodeling decreased.There was no significant difference in MMP-9 and TIMP-1 m RNA expression between Chinese medicine group and captopril group(p>0.05).6.Comparison of RhoA and ROCK protein expression: Compared with the blank group,RhoA and ROCK protein expression water in myocardial tissue of rats in the model group was significantly increased(p<0.05).The expression of RhoA and ROCK protein in captopril group and traditional Chinese medicine group was significantly lower than that in model group(p<0.05);There was no significant difference in RhoA and ROCK protein expression between Chinese medicine group and captopril group(p>0.05).Conclusion:1.Astragalus warm heart formula can improve the cardiac function of HF rats,relieve myocardial injury,inhibit myocardial fibrosis,delay ventricular remodeling,and play a protective role on the heart.Its effect is equivalent to captopril.2.Astragalus warm heart formula can improve ventricular remodeling in HF rats by down-regulating MMP-9 and up-regulating TIMP-1 and inhibiting the over-activation of RhoA/ROCK signaling pathway,which is equivalent to captopril. |
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