主动免疫AT_1受体对自发性高血压大鼠血管重构的影响  

Influence of Active Immunization Against Angiotensin Ⅱ Receptor Type 1 (AT_1)on Hypertension and Remodelingof Mesenteric Arteries in Spontaneous Hypertensive Rats

作　　者：李留东[1] 廖玉华[1] 周子华[1] 魏芬[1] 王敏[1] 王彬[1] 魏宇淼[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心血管疾病研究所,湖北武汉430022

出　　处：《高血压杂志》2005年第5期296-300,共5页Chinese Journal of Hypertension

摘　　要：目的观察血管紧张素Ⅱ的Ⅰ型(AT1)受体细胞外不同肽段主动免疫自发性高血压大鼠(SHR)对血压及血管重构的影响。方法2月龄SHR在血压升高后,以合成的AT1受体细胞外的多肽片段ATR12185、ATR10014和ATR12181作为抗原,分别主动免疫,用药组给予氯沙坦(10mg/(kg·d))灌胃。同龄Wistar大鼠免疫干预组同SHR,对照组只用免疫佐剂。ELISA法检测抗体滴度,大鼠尾动脉血压计测量血压。试验结束前,测定肠系膜三级动脉中层及内径,观察肠系膜动脉病理改变,以及胸主动脉超微病理结构改变。结果SHR于2月龄血压开始升高;所有免疫组动物均产生了针对特定短肽的抗体。ATR12181免疫组SHR收缩压于免疫后1月降低,并持续至实验结束[(145.4±8.5)mmHg,n=7],与SHR对照组[(197.0±7.7)mmHg,n=7,P<0.05]相比,收缩压降低,与氯沙坦治疗组[(139.3±17.2)mmHg,n=7,P>0.05]相比,无显著性差异,而ATR12185和ATR10014免疫组SHR收缩压无明显变化。Wistar大鼠免疫前后收缩压无明显变化。ATR12181免疫组SHR肠系膜三级动脉中膜厚度/管腔半径(1.10±0.18)及中膜面积/管腔面积(3.21±0.98),分别较SHR对照组(1.39±0.21)及(4.62±1.21)降低。结论用ATR12181主动免疫SHR,可降低SHR血压,降低肠系膜三级动脉中膜厚度/管腔半径及中膜面积/管腔面积,逆转主动脉超微结构的损害。ObjectiveTo study the influence of active immunization withdifferent peptides from the extracellular parts of AT1 receptor on the development of hypertension and remodeling of mesentery arteries in spontaneous hypertensive rats (SHR).MethodsMale SHR of 2 months age were allocated into 5 groups and Wistar rats were divided into 4 groups at random. SHR and Wistar rats were immunized actively with antigens, the synthesized peptides(ATR 12185, ATR 10014, ATR 12181) from the extracellular parts of AT 1 receptor, while another SHR group(SHR-L) was given losartan (10 mg/kg·d) by gastric gavage once a day.The specific antibodies were detected by ELISA. Blood pressure (BP) was measured by the tail-cuff method.Wall/lumen area ratio of mesenteric arteries (3rd grade branch) was calculated by computer image analysis system.ResultsAll SHR and Wistar rats were immunized and developed positive antibody titers.At the end of the experiment, compared with control SHR.SHR immunized against ATR12181 had lower systolic blood pressure (145.4±8.5 vs 197.0±7.7) mm Hg (P<0.05).However, no changes in blood pressure immunized against ATR12185 and ATR10014.The normotensive Wistar rats immunized against three peptides, ATR12181, ATR12185 and ATR10014 did not show any change in blood pressure in comparison with non-immunized Wistar controls.Wall-to-lumen area ratio of mesenteric arteries in SHR-L group and SHR immunized group with ATR12181 were significantly decreased compared with SHR control group (P<0.05).The ultrastructure change in thoracic aorticin SHR immunized group with ATR12181 was similar to that of SHR-L(losartan treatment group).ConclusionThe results indicated that long-term immunized with ATR12181 effectively reduced BP in SHRand ameliorated the remodelingof thoracic aorticand mesenteric arteries.

关 键 词：自发性高血压 大鼠 血压 主动免疫 血管紧张素Ⅱ 氯沙坦 

分 类 号：R544.1[医药卫生—心血管疾病]