氯沙坦对肾性高血压大鼠血管中ACE2 mRNA和蛋白质表达水平的影响  

Effect of losartan on the expression of angiotensin-coverting enzyme 2 mRNA and protein in renovascular hypertensive rats

作　　者：林杰[1] 田海红 秦旭平[3] 郑兴[3] 陈临溪[3] 

机构地区：[1]湖南省郴州市第一人民医院北院(儿童医院)药剂科,湖南郴州423000 [2]山西省长治市清华医院,山西长治046001 [3]南华大学药物药理研究所,湖南衡阳421000

出　　处：《中南药学》2010年第1期6-10,共5页Central South Pharmacy

基　　金：湖南省自然科学基金(编号:05JJ30042);湖南省卫生厅课题基金(编号:B2005172)

摘　　要：目的观察血管紧张素转换酶2(ACE2)在两肾一夹高血压大鼠(2K1C)血管中的表达以及氯沙坦对其干预后ACE2 mRNA和蛋白质表达水平的影响。方法建立两肾一夹高血压大鼠模型,用夹尾法测定血压。在实验结束时,使用磷酸盐缓冲溶液对大鼠进行灌注,再用4%多聚甲醛在体灌注,剪取胸主动脉,10%福尔马林中保存进行形态学分析。RT-PCR和Wester-blot分别测定血管组织中ACE2 mRNA及蛋白质表达水平。结果肾动脉狭窄大鼠血压较假手术大鼠明显升高(P<0.01),肾性高血压大鼠较正常大鼠ACE2显著降低(P<0.01)。氯沙坦能剂量依赖性的显著降低血压(P<0.05),减少大鼠主动脉管壁厚度(P<0.01),剂量依赖性地增加ACE2 mR-NA和蛋白质的表达(P<0.05)。结论氯沙坦降低血压和逆转高血压血管重构的机制可能与增加ACE2表达有关。Objective To investigate the expression of ACE2 mRNA and protein in the two kidney-one-clip （2K1C） hypertensive rats. Methods 2K1C hypertensive rat model was used in the experiment, and the blood pressure was measured by tail-cuff method. At the end of the experiment, the whole body of one part of rats was perfused with phosphate buffer saline and followed by fixed in situ with the 4% paraformaldehyde, aortic and mesenteric artery sections were sheared and preserved in 10% formalin for morphological analysis. The protein level of ACE2 was determined by Western-blot. The expression of ACE2 mRNA was detected by RTPCR in thoracic aorta. Results Chronic administration of losartan caused a dose-dependent depressive effect on the blood pressure and hypertrophic artery in 2K1C hypertensive rats （P〈0. 01）. ACE2 level in the mRNA and protein significantly increased in the non treated hypertensive rats compared with the sham operation rats （P〈0.01）. The medium thickness of mesenteric arteries in the losartan treated hypertensive rats significantly decreased compared with the non treated ones. Conclusion The effect of losartan on the hypertension and regression of vascular remodeling is related to the increase of ACE2 expres sion.

关 键 词：氯沙坦 哌唑嗪 血管重构 血管紧张素转换酶2 

分 类 号：R965.1[医药卫生—药理学]