OBJECTIVE To investigate the dose-and time-effect of astragaloside Ⅳ(xylose-glucose-cyclo-astragenol,XGA) on cardiac collagen in rats with acute myocardial infarction and to study its possible mechanisms.METHODS One hundred and twenty-five Wistar rats were randomly divided into groups,among which 8 into the control group,9 into the sham-operated group(8 survived),108 had their left anterior descending branch of coronary artery ligated(operative group),the survivors were randomly divided into ischemic group(n=8) and XGA group(n=64).After XGA administration with different doses and different action times,the serum concentration of angiotensinⅡ(AngⅡ),endothelin(ET),carboxyterminal procollagen typeⅠ propeptide(Ⅰ-CTP) and aminoterminal procollagen type Ⅲ propeptide(P-Ⅲ-NP) in rats were measured,the alteration of myocardial collagen was observed with Masson's stain,and the expression level of matrix metalloproteinases(MMP-2,MMP-9) and its tissue inhibitor of metalloproteinase(TIMP-1) in myocardial tissue were detected with immunohistochemistry methods.RESULTS The serum levels of AngⅡ,ET,I-CTP,and P-Ⅲ-NP increased and the ratio of MMPs/TIMP in ischemic and non-ischemic area decreased in ischemic group compared with those of normal and sham-operated group(P<0.01).After XGA administration with different doses,the serum levels of P-Ⅲ-NP,Ⅰ-CTP,AngⅡ,and ET in all the groups but in the 0.5 mg·kg-1 group decreased significantly and the ratio of MMPs/TIMP in the 5 mg·kg-1 group and the 10 mg·kg-1 group increased markedly compared with those of ischemic group(P<0.05),and the above changes increased gradually with increasing of XGA doses.After XGA administration at a dose of 10 mg·kg-1,the serum index except for the serum level of ET and the ratio of MMPs/TIMP after 7 d treatment decreased markedly and the ratio of MMPs/TIMP increased significantly compared with those of ischemic group(P<0.01),and the above alteration increased gradually with prolonging of action times of XGA.CONCLUSION XGA could reduce myocardial collagen synthesis and increase cardiac collagen degradation,which had the dose-and time-dependented relationships.
LIN Yi;NING Xin-feng;YU Wen;LI Zi-pu.
Effects of Astragaloside Ⅳ on Cardiac Collagen Content in Rats with Acute Myocardial Infarction and Its Mechanisms [J]. Chinese Pharmaceutical Journal, 2008, 43(11): 833-837
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