Effects Of Astragaloside â…£ On Cardiac Collagen In Acute Myocardial Infarction Rats And The Mechanisms

Objective To investigate the dose- and time-effect of astragaloside IV (XGA) on cardiac collagen in acute myocardial infarction rats and to study its possible mechanisms.Methods Totally 88 male Wistar rats of cleaning grade were included in the study, which were randomized into four groups: the control group (n=8), the sham-operation group (n=8), the ischemic group (n=8), and the astragaloside IV group (n=64). The left anterior descending coronary arteries of the rats in ischemic group and astragaloside IV group were ligated, while no ligatation to the coronary arteries but only thoracotomy had been performed to the rats in the sham-operation group. The rats in the astragaloside IV group were randomized into eight groups and began to accept astragaloside IV treatment in different doses (0.5, 2.5, 5.0, 10.0mg/kg/d for 4 weeks) and for different courses of treatment (10.0mg/kg/d for 1, 2, 3, 4 weeks). The serum concentrations of angiotensin â…¡, endothelin, â… -CTP and P-â…¢-NP were measured with Enzyme-Linked immunosorbant assay (ELISA) test at the end of the second and the fourth week. At the end of the fourth week, the left ventriculars of the rats were separated and fixed with neutral formalin, and the expression of collagens, MMP-2, MMP-9 and TIMP-1 in both ischemic and non-ischemic area of hearts was assessed with immunohistochemical methods.Results â‘  XGA decreased the collagen content in hearts of Ml rats. â‘¡ XGA decreased the concentration of angiotensin â…¡, endothelin, â… -CTP and P-â…¢-NP in serum of the MI rats. â‘¢ XGA decreased the expression of MMP-2, MMP-9, and increased the TIMP-1 expression in the myocardium of the MI rats. â‘£ XGA limited the ischemic damage to myocardium of the MI rats. ⑤ The improvement of collagen synthesis was related with the dose and the action time of XGA.Conclusions â‘  XGA could markedly reduce myocardial collagen content and protect the myocardium from ischemic damage. â‘¡The effect on reducing myocardial collagen content gradually increased with the increased dose and the prolonged action time of XGA. â‘¢ The comprehensive regulation such as the angiotensin â…¡, endothelin, Ca²⁺, and the MMPs/TIMPs system, etc., may be in charge of the reduce of cardiac collagen synthesis.