摘要
目的:观察血管紧张素Ⅱ的Ⅰ型(AT1)受体细胞外的不同肽段主动免疫自发性高血压大鼠(SHR)对血压、心脏及血管的影响。方法:2月龄SHR ,随机分成5组,以合成的AT1受体胞外3个多肽片段分别免疫,其余2组为氯沙坦灌胃组( 10mg/ (kg·d) ,标记为SHR L)和对照组(SHR C)。同龄Wistar大鼠免疫干预同SHR ,对照组用免疫佐剂。ELISA法检测抗体滴度,大鼠尾动脉血压计测量血压。试验结束检测心脏及左心室重量、肠系膜三级动脉中层及内径和组织病理变化、心肌超微病理变化。结果:SHR 2月龄血压开始升高,所有免疫组动物均产生针对特定短肽的抗体。ATR12 181免疫组SHR收缩压于免疫后一个月降低,并持续至实验结束( 14 5 4 2±8 4 6mmHg ,n =7) ,与SHR C( 197 0 0±7 70mmHg ,n =7,P <0 0 5 )相比明显降低,与SHR L( 139 2 8±17 19mmHg ,n =7,P >0 0 5 )相比无显著性差异;而ATR12 185和ATR10 0 14免疫组SHR收缩压无明显变化。与SHR C相比,ATR12 181免疫组心脏/体重比( 4 6 6±0 5 0mg/gvs 5 16±0 11mg/g ,P <0 0 5 )和左心室/体重比( 3 6 4±0 4 5mg/gvs 4 19±0 0 7mg/g ,P <0 0 5 )均显著降低;而ATR12 181免疫组与SHR L心脏/体重比( 4 4 1±0 6 0mg/g)及左心室/体重比( 3 5 0±0 31mg/g)相比无显著性差异。
Objective:To study the influence of active immunization with different peptides from the extracellular parts of AT 1 receptor on hypertension development and protection effect for heart and mesentery arteries in spontaneous hypertensive rats(SHR).Methods:Male SHR of 2 months age were divided 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 from the extracellular parts of AT 1 receptor,while another SHR group was given losartan(10 mg/(kg·d)) orally by gastric gavage once a day.The specific antibodies were detected by ELISA and blood pressure(BP) was measured by the tail-cuff method.Wall-to-lumen area of rations of mesenteric arteries(3rd grade branch) was calculated by computer image analysis system.The level of heart hypertrophy was assessed by the heart wight to body weight and left ventricular weight to body weight ratio.Results:All SHR and Wistar rats immunized against the peptides developed positive antibody titers after the second immunization.At the end of the experiment,SHR immunized against ATR12181 had lower systolic blood pressure(145 42±8 46 mmHg, n =7) than SHR-C(197 00±7 70 mmHg, n =7).However,no changes has been observed in blood pressure immunized against ATR12185 and ATR10014.The 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 of rations of mesenteric arteries in SHR-L(1 05±0 12, n =7) group and SHR immunized group with ATR12181(1 10±0 18, n =7) were significantly decreased compared with SHR control group(1 39±0 21, n =7, P <0 05).The ultrastructure change in heart in SHR immunized group with ATR12181 was similar with SHR-L group.Conclusion:The results indicated that long-term immunized with ATR12181 effictively reduced BP of SHR,attenuated and regressed the resistant vessel and heart hypertrophy.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2005年第5期372-376,共5页
Chinese Journal of Immunology
基金
国家自然科学基金资助项目 (批准号No G3 0 3 0 0 13 3 )
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
Spontaneously hypertensive rats
Blood pressure
Active immunization
Angiotensin
Losartan
