摘要
目的 :通过新内皮素受体拮抗剂CPU 0 2 13对左 甲状腺素 (L thy)诱导的大鼠肥大心肌中基质金属蛋白酶 (MMPs)的改变 ,探讨内皮素参与诱导心肌肥大和细胞外基质改变的机制。方法 :雄性SD大鼠随机分成 3组 ,除对照组外 ,大鼠每日给予L thy (sc ,0 .4mg/kg)共 10d ,药物干预组在第 7天时给新型内皮素受体拮抗剂CPU 0 2 13(po ,10 0mg/kg) ,连续 3d。动物处死后取大鼠心脏测定心肌组织中总胶原含量、MDA的含量及SOD活性。大鼠左心室的MMPs的活性由明胶酶谱法测定 ,Ⅰ型胶原基因 (proα2 (Ⅰ )collagen)的基因表达由半定量RT PCR方法确定。结果 :L thy心肌病组大鼠心肌中的总胶原含量减少 ,SOD活性下降 ,MDA含量增多 ,MMPs的活性被抑制。RT PCR结果显示L thy组的大鼠左心室proα2 (Ⅰ )collagen的基因表达下调。给予CPU 0 2 13干预后大鼠心肌总胶原含量及SOD活性上升 ,MDA含量减少 ,大鼠左心室中MMPs活性被抑制 ,左心室中proα2 (Ⅰ )collagen的基因表达上调。结论 :L thy诱导的大鼠心肌肥大是一种缺少纤维化的肥大 ,肥大心肌中自由基增多且脂质膜受损。内皮素 1(ET 1)参与介导心肌MMPs活性的调节 ,新内皮素受体拮抗剂CPU 0 2 13能明显上调proα2(Ⅰ )
AIM:To study the activity alteration of matrix metalloproteinases (MMPs) in the rat cardiomyopathy induced by L thyroxine and involved mechanism. METHOD: Male Sprague Dawley rats were randomly divided into three groups and administrated suspension of L thyroxine (sc,0.4 mg/kg·d -1 ) for consecutive 10 d except for normal group. L thyroxine treated rats were given CPU 0213(po, 100 mg/kg·d -1 )in group CPU 0213 for 3 d. The whole collagen content, MDA and SOD in myocardium were measured. Relative left ventricular activity level of MMPs was determined by substrate zymography. Furthermore, relative left ventricular mRNA level of proα2 (Ⅰ) collagen were detected with semi quantitative RT PCR. RESUIT: The whole collagen content and proα2 (Ⅰ) collagen mRNA expression were decreased in L thyroxine group and increased in the group CPU 0213. In L thyroxine group the activity of SOD was decreased but increased in CPU 0213 group and the content of MDA in L thyroxine group was increased but decreased in CPU 0213 group. The activity of MMPs (MMP 2, MMP 9) was downregulated in L thyroxine group and CPU 0213 group had litter effect on the activity of MMPs. CONCLUSION:Myocardial hypertrophy induced by L Thyroxin, a kind of cardiac hypertrophy that is accompanied by less cardiac fibrosis is mediated partly by ET 1. In L thyroxine induced hypertrophic myocardium oxidative stress is enhanced. CPU 0213 could inhibit oxidative stress and increase collagen content. The hypertrophic myocardium mechanic induced by L thyroxine was related to ET 1.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2004年第2期150-155,共6页
Journal of China Pharmaceutical University
基金
国家自然科学基金重点课题资助项目 (No .3 0 2 3 0 170 )~~
