Objective To investigate the effects of astragaloside Ⅳ (XGA) on metabolism of cardiac collagen in rats and its possible mechanisms.Methods The myocardial fibroblast cells (FBC) were isolated from rats by collagenase and trypsinase digestion method,and cultured stably.After incubation with different concentrations of XGA for various durations,the mRNA expression levels of typeⅠ,Ⅱ,Ⅲ collagens,matris metalloproteinase-1 (MMP-1),MMP-2,MMP-9,tissue inhibitor of metalloproteinase-1 (TIMP-1),and TIMP-2 in the cells were measured.The rat models of acute myocardial infarction were induced by ligation of left anterior descending coronary artery and the survivors were randomly divided into ischemic group and XGA group;meanwhile,normal group and sham-operated group were also established.After administration of different doses of XGA (0.5-10.0 mg/kg)for various durations (7-28 d),the serum concentrations of angiotensinⅡ (AngⅡ),endothelin (ET),carboxyterminal procollagen typeⅠpropeptide (Ⅰ-CTP) and aminoterminal procollagen typeⅢpropeptide (P-Ⅲ-NP) were measured.The alteration of myocardial collagen was observed with Masson’s staining,and the expression levels of MMP-2,MMP-9,and TIMP-1 in myocardial tissue were detected immunohistochemically.Results XGA reduced the mRNA expression levels of typeⅠ,Ⅲ and Ⅳ collagens,TIMP-1,and TIMP-2,and elevated the mRNA expression levels of MMP-1,MMP-2,and MMP-9 in FBC in a concentration-and time-dependent manner.After XGA administration,the serum levels of P-Ⅲ-NP,Ⅰ-CTP,AngⅡ,and ET decreased significantly in all dose groups except 0.5mg/kg group,and the ratio of MMPs/TIMP increased markedly in 5 and 10mg/kg groups compared with ischemic group,and the effects were in a dose-dependent manner.Except ET at all predetermined time points and the ratio of MMPs/TIMP on day 7,all the serum indices decreased markedly after XGA administration at a dose of 10 mg/kg,and the ratio of MMPs/TIMP increased significantly;the effects were in a time-dependent manner.Conclusion XGA can markedly reduce the myocardial collagen formation,and the mechanisms are possibly related with its roles in inhibiting collagen synthesis and promoting collagen degradation.?更多