肾性高血压大鼠肥厚心肌中Pyk2表达和激活的变化及缬沙坦的干预研究  

The effects of valsartan on changes of Pyk2 expression and activation in myocardium of renovascular hypertensive rats

作　　者：吴浩[1] 陈清枝[2] 邢淑华[3] 武维恒[1] 祁春梅[1] 

机构地区：[1]徐州医学院第二附属医院心内科,江苏徐州221006 [2]徐州医学院附属医院心内科,江苏徐州221002 [3]徐州医学院药理学教研室,江苏徐州221002

出　　处：《现代医学》2009年第2期100-104,共5页Modern Medical Journal

摘　　要：目的以肾性高血压大鼠为模型，研究心肌中富脯氨酸蛋白酪氨酸激酶（Pyk2）的表达情况，探讨缬沙坦逆转左室重构的可能机制。方法制备两肾一夹肾性高血压大鼠模型，将大鼠随机分为假手术组、模型组和缬沙坦（30mg·kg^-1·d^-1）组，分别于术前及术后第1、4、8和12周测定动脉血压和心肌肥厚指数，用免疫组化法检测心肌组织中Pyk2及磷酸化Pyk2（p-Pyk2）表达。结果术后4周心肌肥大已发生，8—12周心肌肥大进一步加重，缬沙坦能显著降低肾血管性高血压大鼠的血压，并能有效抑制心肌肥厚的形成（P〈0．01）；术后1、4、8和12周大鼠心肌组织Pyk2活性逐渐增加（1周P〈0．05，4、8、12均P〈0．01）；缬沙坦组Pyk2及p—Pyk2表达水平下降，与同周龄模型组相比差异有统计学意义（P〈0．01）。结论Pyk2及p—Pyk2在肾性高血压大鼠心肌组织内表达增高，且与心肌肥厚同步；缬沙坦能下调Pyk2及p—Pyk2的表达。这可能是AT1受体拮抗剂逆转心肌肥厚重构的机制之一。Objective To study the effects of valsartan on ventricular hypertrophy and the expression of Proline-rich tyrosine kinase 2 （Pyk2） in myocardium of renovascular hypertensive rats（RHR）. Methods Two- kidney and one-clip（2K1C） renal hypertensive model was established in Sprague-Dawley rats by chronic partial occlusion of left renal artery. Rats were randomly divided into model-operation group, sham-operation group and valsartan group. Rats in valsartan group received valsartan 30 mg. kg^- 1·d^-1. Left ventricular mass to body mass ratio was measured to assay the degree of myocardial hypertrophy. Expression of Pyk2 protein and tyrosine-phosphorylated Pyk2 （p-Pyk2） were detected by immunohistochemisry. Results Blood pressure （BP）, left ventricular mass to body mass ratio, Pyk2 activity in myocardium of RHR were increased gradually. Valsartan could reverse the high BP level of the model,also the myocardial hypertrophy（P 〈0.01 ）. Pyk2 levels and the amount of p-Pyk2 were measured by Western-Blotting, they were evidently increased in the model-operation group than that of the sham-operation group（ lweek P 〈0.05,4 to 12 weeks P 〈0.01 ）. Pyk2 and p-Pyk2 levels were significantly dicreased in valsartan group than that of their time-matched model-operation groups （P 〈 0. 01 ）. Conclusion Increased expression of Pyk2 and p-Pyk2 in the left ventricle of RHR is probably associated with the progress of the left ventricular hypertrophy （LVH）. The preventive mechanism of valsartan cardiac hypertrophy in RHR is related to the decrease of Pyk2 expression and its activity in cardiac tissue.

关 键 词：富脯氨酸蛋白酪氨酸激酶 心肌肥大 缬沙坦 肾性高血压 大鼠 酪氨酸磷酸化 

分 类 号：R544.14[医药卫生—心血管疾病] R33-33[医药卫生—内科学]