摘要
目的 研究Ⅲ型胶原、基质金属蛋白酶 2 (matrixmetalloproteinases 2 ,MMP 2 )和JNK1/ 2在高血压大鼠心肌组织中的表达及氯沙坦干预后 3者的变化 ,探讨氯沙坦逆转心室重构的药理机制。方法 采用SD大鼠建立两肾一夹型 (Goldblatt)高血压模型 ,将大鼠随机分为对照组、高血压组和氯沙坦治疗组。采用鼠尾动脉测压法记录每周血压变化 ,实验末切取心脏 ,并计算心脏与体重比值。免疫组织化学方法测定心脏组织中的Ⅲ型胶原、基质金属蛋白酶 2和JNK1/ 2表达。结果 左肾动脉结扎术后大鼠收缩压升高 ,心脏体重比值增加 ,心肌间质Ⅲ型胶原、基质金属蛋白酶 2、心肌细胞JNK1/ 2表达增多。氯沙坦治疗能显著降低大鼠收缩压 ,降低心脏体重比值 ,并且使心肌间质Ⅲ型胶原、基质金属蛋白酶 2、心肌细胞JNK1/ 2表达减少。结论 两肾一夹型高血压大鼠重构心肌中MMP 2、Ⅲ型胶原、JNK1/ 2表达升高。氯沙坦能有效逆转心肌肥厚或心室重构 ,这一效应与其降低心肌中高表达的MMP 2 ,Ⅲ型胶原、JNK1/
Objective To investigate the effects of losartan on the expression of matrix metalloproteinases-2, collagen Ⅲ and JNK1/2 in the myocardium of hypertensive rats. Methods Sprague-Dawley rats (220-250 g) were used to create the two kidney one clipped (2K1C) Goldblatt hypertensive rats model. The rats were randomly divided into control group, hypertensive group and losartan treatment group (losartan 20 mg/kg for 6 weeks). Systolic blood pressure (SBP) was recorded, once a week, using the tail-cuff method. The ratio of heart weight (HW) and body weight (BW) was derernined. The expression of matrix metalloproteinases-2, collagen Ⅲ and JNK1/2 was assessed by immunohistochemistry. Results In 2K1C rats, SBP and the ratio of HW/BW were significantly increased compared with control group ( P <0.05). The expression of MMP-2, collagen Ⅲ and JNK1/2 was enhanced in the myocardial tissue. After 6 weeks treatment with losartan, SBP and the ratio of HW/BW were significantly attenuated, as well as the expression of MMP-2, collagen Ⅲ and JNK1/2 in the interstitium and cardiomyocyte. Conclusion In 2K1C rats, the expression of MMP-2, collagen Ⅲand JNK1/2 in heart were elevated. Losartan significantly reversed myocardial hypertrophy which was associated to the reduction of expression of MMP-2, collagen Ⅲ and JNK1/2 in the myocardial tissue in hypertensive rats.
出处
《高血压杂志》
CSCD
2004年第6期551-555,共5页
Chinese Journal of Hypertension
基金
南华大学博士启动基金资助项目(编号 :5 0 3 XJQ 0 3 0 43 )
