氯沙坦对自发性高血压大鼠血管组织激肽释放酶表达的影响

Effect of Losartan on Kallikrein Expression in Spontaneously Hypertensive Rat Aorta

目的探讨氯沙坦对自发性高血压大鼠(spontaneously hypertensive rats,SHR)血管组织激肽释放酶(Kallikrein)表达的影响。方法16只♂SHR大鼠随机分为高血压模型组和氯沙坦组,8只♂Wistar-Kyoto大鼠为正常血压组。无创血压测量仪测量各组收缩压变化;ELISA试剂盒检测血清中Kallikrein、一氧化氮(NO)及前列环素(PGI2)含量变化;HE染色观察药物对主动脉病理学改变;实时定量qRT-PCR检测主动脉组织间Kallikrein基因表达变化;Westernblotting检测主动脉组织中Kallikrein蛋白表达变化。结果SHR大鼠连续给药4周后,氯沙坦组收缩压呈时间依赖性下降;大鼠血清中Kallikrein、NO及PGI2分别上升了54.1%,49.5%,49.2%;组织病理学显示,氯沙坦组血管重构现象明显低于模型组;qRT-PCR显示,氯沙坦组的Kallikrein表达量上调了66.7%;Westernblotting显示氯沙坦组Kallikrein蛋白表达与基因表达一致,呈正相关。结论氯沙坦降低SHR大鼠收缩压及改善血管重构的作用可能与上调Kallikrein表达相关。

OBJECTIVE To investigate the effect of losartan on Kallikrein expression in spontaneously hypertensive rats(SHR).METHODS Sixteen♂SHR rats were randomly divided into hypertension model group and losartan group,while eight♂normotensive Wistar-Kyoto rats was normal blood pressure group.Non-invasive blood pressure measuring instrument monitored systolic blood pressure(SBP)of each group rats in every week.The serum levels of total Kallikrein,NO and PGI2 were measured.Aorta change was evaluated with histopathologic examination by HE staining.qRT-PCR tested the gene expression change of Kallikrein.And the expression of Kallikrein in aortic tissue was measured by Western blotting.RESULTS After 4 weeks of continuous administration in SHR rats,the SBP of the losartan group decreased in a time-dependent manner.The serum levels of Kallikrein,NO and PGI2 in rats increased by 54.1%,49.5%,and 49.2%,respectively.Histopathology showed that the vascular remodeling phenomenon in the losartan group was significantly lower than that in the model group.qRT-PCR showed that the expression of Kallikrein in the losartan group was up-regulated by 66.7%.Western blotting showed that Kallikrein protein expression and gene expression in the losartan group were consistent and positively correlated.CONCLUSION Losartan decreasing SBP and improving vascular remodeling from SHR rats may be related to up-regulation of Kallikrein expression.