抗血管紧张素Ⅱ1型受体抗体对自发性高血压大鼠血压和肾脏的影响

Influence of antibody against AT1 receptor on blood pressure and kidney of spontaneous hypertensive rat

目的观察血管紧张素Ⅱ1型受体(AT1受体)胞外不同肽段主动免疫对自发性高血压大鼠(SHR)血压和肾脏的影响。方法人工合成的AT1受体胞外肽段主动免疫SHR。动态监测SHR血压变化,观察肾脏组织病理变化,RT-PCR法检测肾脏组织原癌基因表达水平。结果ATR12181组血压为(179.0±13.6)mmHg较对照组(188.0±9.9)mmHg下降(P<0.05)。ATR12181组相比对照组肾脏病理变化减轻,ATR11188组相比对照组病变加重。ATR12181组cf-os、cj-un表达水平明显低于对照组(P<0.05),ATR11188组则明显高于对照组(P<0.05)。结论不同肽段免疫产生的不同抗体对SHR血压和肾脏可产生不同的影响。

Objective To observe the influence of active immunization with different peptides from extracellular parts of AT1 receptor on blood pressure and kidney in spontaneous hypertensive rats （SHRs）. Methods SHRs were immunized actively with four types antigens which were different pepfides （ATR12181, ATR13275, ATR11188, and ATR13263） from the extracellular parts of AT1 receptor conjugated to tetanus toxoid （TT）. The systolic blood pressure （SBP） was measured indirectly in conscious rats using tail-cuff plethysmography in week 1, 5, 9, 13, 17, 21, 25. In week 25, all SHRs were sacrificed and kidney specimens were processed for morphological examination by light and electron microscopy. The c-fos and c-jun levels in kidney were detected by RT-PCR. Results In week, 25 SBP of ATR12181 group was significantly decreased [（179.0±13.6） mmHg] compared with control group [（188.0±9.9） mmHg, P 〈 0.05]. The degree of glomerulosclerosis and tubulointexstitial fibrosis was significantly attenuated in ATR12181 group compared with the control group. The ultrastructural impairment of ATR12181 group was significantly alleviated compared with the control group,bnt the impairment those ATR11188 group was aggravated and the deposition was found in mesangial region. The c-fos and c-jun mRNA levels of ATR12181 group were lower than those of the control group （P 〈 0.05）. On the other hand, the c-fos and c-jun mRNA levels of ATR11188 group were higher than those of the control group （P 〈 0.05）. Conclusion Active immunization with different peptides from the extracelluar parts of AT1 receptor have different influence on blood pressure and kidney in SHRs.