摘要
目的 探讨大鼠心肌梗死后心肌间质基质金属蛋白酶 (MMPs)活性和心室重塑的关系及药物氯沙坦干预的影响。方法 Sprague Dawley(SD)大鼠 82只 ,随机分为对照组 (n =10 )、心肌梗死组 (MI组 ,n =36 )和氯沙坦组 (n =36 )。氯沙坦组予氯沙坦 5 0mg·kg-1·d-1灌胃 ,第 2周开始与MI组予异丙肾上腺素。酶谱法测定各组不同时间MMPs活性 ,氯胺T法测定胶原含量 ,免疫组化法测定I/III胶原比例 ,电镜观察心肌超微结构。结果 心肌梗死组MMP 2、MMP 9活性在各周时间点明显升高 ,胶原含量和I/III胶原比例随后升高。而氯沙坦组MMPs活性、胶原含量和I/III胶原比例较MI组显著降低。结论 大鼠心梗后间质内MMPs活性升高 ,继发胶原含量增加 ,I/III胶原比例升高 ,是心室重塑的重要原因。氯沙坦对MMPs活性的影响可能是其干预心梗后心室重塑的机制之一。
Objective To study the relationship of matrix metallproteinases(MMPs) on ventricular remodeling following myocardial infarction in the rats and the intervening effects of losartan. Methods Eighty-two Sprague-Dawley(SD) rats were randomly divided into the groups of control (group C, n=10), myocardial infarction (group MI, n=36) and losartan group (LT , n=36), the rats of group LT were given losartan 50mg·kg -1 ·d -1 orally and the rats of group LT and group MI were given isoprenaline(ISP)from the second week of the study. The activity of MMPs was measured by zymography and collagen amount by the method of chloramine T, the ratio of I/III collagen was assessed by immunohistochemical stain. The microstructure of myocardium was observed with electron microscope. Results The activities of MMP-2 and MMP-9 in the group MI increased significantly at the 1st, 2nd (P<0.01) and 4th week (P<0.05) after MI. The collagen amount and I/III collagen ratio increased subsequently. The activity of MMP-2 in the group LT reduced significantly at the 1st, 2nd (P<0.01)and 4th week(P<0.05) after the onset of study compared with that of group MI. Also did MMP-9's activity at the 1st week (P<0.01) and at 2nd and 4th week (P<0.05). The collagen amount and I/III collagen ratio decreased accordingly. Conclusion The activity of MMPs in the myocardial interstitium increased following myocardial infarction, then collagen amount raised and I/III collagen ratio increased. These changes may be the major causes of ventricular remodeling. The effects of losartan on the activity of MMPs may be one of mechanisms on the ventricular remodeling following myocardial infarction.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2003年第3期223-225,共3页
Chinese Journal of Cardiology
基金
浙江省教育厅资助项目 ( 2 0 0 10 36 0 )
