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中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (11): 1226-1230.

• 基础研究 • 上一篇    下一篇

ATR12181 降压疫苗降低自发性高血压大鼠的尿微量白蛋白作用

魏芬, 廖玉华, 李留东, 周子华, 王彬, 王敏   

  1. 华中科技大学同济医学院附属协和医院心内科, 武汉430022, 湖北
  • 收稿日期:2007-03-10 修回日期:2007-10-29 发布日期:2020-11-04
  • 通讯作者: 廖玉华, 男, 教授, 博士生导师, 主要从事心血管病免疫学研究。Tel:027-85726013 E-mail: liaoyh27@163.com
  • 作者简介:魏芬, 女, 心内科博士研究生, 研究方向:心血管病免疫学。Tel:027-63757216 E-mail: Weifen2002@hotmail.com
  • 基金资助:
    国家自然科学基金资助项目(30300133)

ATR12181 vaccine in reducing microalbuminuria of spontaneously hypertensive rat

WEI Fen, LIAO Yu-hua, LI Liu-dong, ZHOU Zi-hua, WANG Bin, WANG Min   

  1. Institute of Cardiology,Union Hospital,Tongji Medical College,Huazhong University of Science &Technology,Wuhan 430022,Hubei,China
  • Received:2007-03-10 Revised:2007-10-29 Published:2020-11-04

摘要: 目的: 研究血管紧张素Ⅱ受体I 型(AT1) 胞外的肽段ATR12181 主动免疫自发性高血压大鼠(SHR) 后是否降低尿微量白蛋白。方法: 根据大鼠AT1 受体胞外肽段氨基酸序列设计合成的多肽片段ATR12181 作为抗原主动免疫SHR 和WISTAR 大鼠,SHR 用药组给予氯沙坦(10 mg·kg-1·d-1) 灌胃治疗, 动态监测血清抗体滴度及收缩压, 以ELISA 法检测尿微量白蛋白, RT-PCR 法检测肾脏组织中AT1R、c-fos、c-jun 基因表达。结果: ATR12181 免疫SHR 后产生高滴度抗体并降低血压, 20 周末收缩压为(145±8) mm Hg(1 mm Hg =0.133 kPa),低于SHR 对照组(197 mm Hg±8 mm Hg, P<0.05),与氯沙坦组相近(139 mm Hg±17 mm Hg, P>0.05); WISTAR 大鼠免疫后产生高滴度抗体, 血压正常(116 mm Hg±6 mm Hg) 。ATR12181 主动免疫组SHR 尿微量白蛋白降低, 肾脏AT1R、c-fos、c-jun 基因表达下调, 与氯沙坦组变化相近(P>0.05),低于SHR 对照组(P<0.05) 。WISTAR 大鼠免疫组与正常对照组相比无改变。结论: 用AT1 胞外肽段ATR12181 主动免疫SHR 可产生高滴度抗体, 降低血压和尿微量白蛋白。正常大鼠免疫后可产生高滴度抗体, 但对机体无影响。

关键词: 自发性高血压大鼠, ATR12181 降压疫苗, 肾脏, 尿微量白蛋白

Abstract: AIM: To evaluate effect of active immunization with peptide ATR12181 from the extracellular parts of AT1 receptor on reducing microalbuminuria of SHRs. METHODS: SHRs and Wistar rats were immunized actively by ATR12181, the synthesized peptide from the extracellar part of AT1 receptor. Another SHR group was given Losartan (10 mg·kg-1·d-1) orally by gastric gavage once a day in morning. The specific serum antibody titer and 24h urinary albumin excretion were detected by ELISA, the Systolic Blood Pressure(SBP) of SHR was measured consecutively, and the mRNA of AT1R, cfos, c-jun in kidney were measured by RT-PCR. RESULTS: The antibodies to ATR12181 were detected both in immulized SHRs (SHR-I) and WISTAR rats (WISTAR-I). At 20 weekends, SHR-I group got a lower SBP (145 mm Hg±8 mm Hg) than SHR-C group (197 mm Hg±8 mm Hg),but no significant difference compared with the SHR-L group (139 mm Hg±17 mm Hg, P>0.05). The SBP of WISTAR-I group was normal (116 mm Hg±6 mm Hg). 24 h urinary albumin excretion both in SHR-I group and SHR-L group were significantly lower than that of SHR-C group (P< 0.05); The mRNA of the AT1R, c-fos, c-jun were significantly lower in SHR-I group and SHR-L group. CONCLUSION: ATR12181 vaccine may produce high titer antibody, that reduce the blood pressure, and decrease urinary protein excretion in SHR.

Key words: spontaneously hypertensive rats, ATR12181 vaccine, kidney, microalbuminuria

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