ATR12181降压疫苗降低自发性高血压大鼠的尿微量白蛋白作用

ATR12181 vaccine in reducing microalbuminuria of spontaneously hypertensive rat

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(10mg·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)mmHg(1mmHg=0.133kPa),低于SHR对照组(197mmHg±8mmHg,P<0.05),与氯沙坦组相近(139mmHg±17mmHg,P>0.05);WISTAR大鼠免疫后产生高滴度抗体,血压正常(116mmHg±6mmHg)。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。

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 serrum 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, c-fos, c-jun in kidney were measured by RT-PCR. RE- SULTS： Tne antibodies to ATR12181 were detected both in immulized SHRs （SHR-I） and WISTAR rats （WIST- AR-I）. At 20 weekends, SHR-I group got a lower SBP （ 145mmHg - 8mmHg） 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 Hg6 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） ; qlae mRNA of the AT1R, c-fos, c-jun were significantly lower in SHR-1 group and SHR-L group. CON- CLUSlON： ATR12181 vaccine may produce high titer antibody, that reduce the blood pressure, and decrease urinary protein excretion in SHR.