黄芪皂苷Ⅳ对急性心肌梗死大鼠心肌胶原含量的影响

Effects of Astragaloside Ⅳ on Cardiac Collagen Content in Rats with Acute Myocardial Infarction and Its Mechanisms

目的研究黄芪皂苷Ⅳ(xylose-glucose-cyclo-astragenol,XGA)对急性心肌梗死(MI)大鼠心肌胶原代谢的影响及机制。方法125只Wistar大鼠随机分组,其中108只手术结扎左冠状动脉(手术组),存活者随机分为缺血组(8只)和XGA组(64只);9只列入假手术组(8只存活),8只列入正常组。给予XGA组不同剂量和不同作用时间的XGA,观察血清Ⅲ型前胶原氨基端肽(P-Ⅲ-NP)、Ⅰ型前胶原羧基端肽(Ⅰ-CTP)、血管紧张素Ⅱ(AngⅡ)和内皮素(ET)的变化,Masson染色观察心肌组织胶原情况,免疫组化法观察心肌组织MMP-2、MMP-9及TIMP-1的表达。结果缺血组大鼠血清P-Ⅲ-NP、Ⅰ-CTP、AngⅡ及ET的含量均明显高于正常组和假手术组(P<0·01),心肌缺血区和非缺血区的MMPs/TIMP比值则明显下降(P<0·01)。给予不同剂量XGA后,除0·5mg·kg-1剂量组外,其余各组血清P-Ⅲ-NP、Ⅰ-CTP、AngⅡ、ET含量均较缺血组明显下降(P<0·05),同时5和10mg·kg-1剂量组心肌MMPs/TIMP比值较缺血组明显增加;且上述变化与XGA剂量呈剂量依赖性。给予缺血大鼠XGA10mg·kg-1,除血清ET水平和心肌MMPs/TIMP比值在治疗7d后与缺血组变化不大外(P>0·05),其余各组血清指标较缺血组明显下降(P<0·01),心肌MMPs/TIMP比值较缺血组明显增加(P<0·01),且上述变化与XGA用药时间呈时间依赖性。结论XGA可减少心肌胶原合成,增加心肌胶原降解,且具有一定的量效和时效关系。

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 twentyfive 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 angiotensin Ⅱ （ Ang Ⅱ ） , endothelin （ET） , carboxyterminal procollagen type I propeptide （Ⅰ-CTP） and aminoterminal procollagen type Ⅲ propeptide （P-BI-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-Ⅰ） in myocardial tissue were detected with immunohistochemistry methods. RESULTS The serum levels of Ang Ⅱ , ET, Ⅰ- CTP, and P-HI-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-IR- NP, ｜-CTP, Ang Ⅱ, 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 isehemic 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.