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引用本文:杨小虎,吕莎,彭应枝,余杨,岳影星,张勇.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[J].中国现代应用药学,2020,37(18):2206-2210.
YANG Xiaohu,LYU Sha,PENG Yingzhi,YU Yang,YUE Yingxing,ZHANG Yong.Effect of Losartan on Kallikrein Expression in Spontaneously Hypertensive Rat Aorta[J].Chin J Mod Appl Pharm(中国现代应用药学),2020,37(18):2206-2210.
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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
杨小虎,吕莎,彭应枝,余杨,岳影星,张勇
1.浙江医院药剂科, 杭州 310030;2.浙江省老年医学重点实验室和老年医学研究所, 杭州 310013;3.湖北医药学院药学院, 湖北 十堰 442000
摘要:
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;Western blotting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%;Western blotting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。
关键词:  氯沙坦  高血压  血管重构  激肽释放酶
DOI:10.13748/j.cnki.issn1007-7693.2020.18.006
分类号:R965.1
基金项目:浙江医院院级课题项目(2015YJ038)
Effect of Losartan on Kallikrein Expression in Spontaneously Hypertensive Rat Aorta
YANG Xiaohu1, LYU Sha1, PENG Yingzhi1, YU Yang1, YUE Yingxing2,3, ZHANG Yong4
1.Department of Pharmacy, Zhejiang Hospital, Hangzhou 310030, China;2.Zhejiang Provincial Key Laboratory of Geriatrics&3.Geriatrics Institute, Hangzhou 310013, China;4.College of Pharmacy, Hubei University of Medicine, Shiyan 442000, China
Abstract:
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.
Key words:  losartan  hypertension  vascular remodeling  Kallikrein
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