摘要
【目的】研究肾性高血压大鼠 (renalhypertensiverats ,RHR)心肌肥大发生发展过程中心肌组织丝裂原活化蛋白激酶 (MAPK)活性、蛋白表达及丝裂原活化蛋白激酶磷酸酶 (MKP 1)蛋白表达的变化以及血管紧张素Ⅱ (AngⅡ ) 1型受体(AT1)拮抗剂TCV116作用。【方法】①制作两肾一夹肾性高血压大鼠模型 ;②以左心室质量与体质量比值作为心肌肥大的指标 ;③以胶内MBP原位磷酸化法测定MAPK活性 ,以免疫印迹法检测MKP 1蛋白表达。【结果】①大鼠肾动脉狭窄术后 8周心肌肥大已发生 ,12周至 16周心肌肥大进一步加重 ;②术后 8周、12周、16周大鼠心肌组织MAPK活性逐渐增加 ,各周龄组MKP 1蛋白表达虽然均高于同周龄对照组 ,但随肾动脉狭窄时间延长呈下降趋势 ,心肌MAPK活性与心肌肥大程度呈显著正相关 ,而与MKP 1蛋白表达呈显著负相关。③TCV116可有效抑制心肌肥大及MAPK活性、MKP 1蛋白表达的变化。【结论】AngⅡ是介导两肾一夹肾性高血压大鼠心肌肥大的重要因子 ;AngⅡ主要通过AT1受体介导心肌肥大反应及MAPK激活 ;MAPK是心肌肥大的重要信号通路 ,随肾动脉狭窄时间的延长 ,MKP 1表达逐渐下降可能是导致MAPK持续激活并导致心肌肥大加剧的重要原因。
Objective To investigate the relationship between MKP 1 and MAPK and the effect of TCV 116, an AT 1 receptor antagonist, on the changes of MAPK and MKP 1 in myocardial hypertrophy of renovascular hypertensive rats (RHR). Methods ①Two kidney and one clip renal hypertensive model was established in Sprague Dawley rats by chronic partial occlusion of left renal artery; ② Left ventricular mass to body mass ratio was measured to assay the degree of myocardial hypertrophy; ③ MAPK activity was examined using an in gel kinase assay, MKP 1 protein expression was detected by western blotting. Results ① Blood pressure, left ventricular mass to body mass ratio, MAPK activity in myocardium of RHR were increased gradually, but the increment of MKP 1 protein expression tended to dropping from 8th to 16th week after renovascular constriction. ② There was a significantly positive correlation between MAPK activity and myocardial hypertrophy, but a significantly negative correlation between MAPK activity and MKP 1 protein expression. ③ TCV116 effectively inhibited myocardial hypertrophy and prevented changes of MAPK activity and MKP 1 protein expression in RHR. Conclusion Angiotensin Ⅱ is an important factor in myocardial hypertrophy in RHR, which mediates the hypertrophic responses and activation of MAPK mainly through AT 1 receptor. The MAPK pathway is important for the development and intensification of myocardial hypertrophy by the long term activation of MAPK, and the regulation of MKP 1 on MAPK may play an important role in the development of myocardial hypertrophy in RHR.
出处
《中山医科大学学报》
CSCD
2000年第2期87-91,共5页
Academic Journal of Sun Yat-sen University of Medical Sciences
基金
国家自然科学基金! ( 3 9870 888)
关键词
MAPK
MKP-1
肾性高血压
心肌肥大
mitogen activated protein kinase (MAPK)
mitogen activated protein kinase phosphatase 1(MKP 1)
cardiomyopath, hypertrophic
hypertension, renal
rats
