血管紧张素AT1受体短肽主动免疫对自发性高血压大鼠血压及靶器官的影响

Effect of active immunization with AT1 receptor peptides on blood pressure and cardiovascular remodeling in spontaneous hypertension rats

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对自发性高血压大鼠(SHR)血压及 靶器官的影响。方法:8周龄SHR随机分成免疫组,氯沙坦治疗组及SHR对照组。免疫组分别以合成的AT1受体细 胞外多肽片段ATR12181、ATR12185及ATR10014主动免疫;氯沙坦治疗组给予氯沙坦(10mg·kg-1·d-1)灌胃,而 对照组只用免疫佐剂。同龄Wistar大鼠亦分为免疫组(干预方法同SHR)及对照组(用免疫佐剂)。免疫后每个月 ELISA法检测免疫组动物的抗体滴度,用大鼠尾动脉血压计观察大鼠血压。试验7个月检测心脏及左心室质量、组织 病理变化及心肌超微病理变化。结果:免疫组动物均产生针对特定短肽的抗体。ATR12181免疫组SHR收缩压于免 疫后1个月开始至实验结束逐渐降低,与SHR对照组相比收缩压明显降低,与氯沙坦治疗组相比收缩压差异无统计 学意义(P>0.05);而ATR12185和ATR10014免疫组SHR收缩压无明显变化。与SHR对照组相比,ATR12181免疫 组SHR心脏/体重比((4.66±0.50)mg/gvs(5.16±0.11)mg/g,P<0.05)和左心室/体重比((3.64±0.45)mg/gvs (4.19±0.07)mg/g,P<0.05)均显著降低;与氯沙坦治疗组心脏/体重比((4.41±0.60)mg/g)及左心室/体重比 ((3.50±0.31)mg/g)相比差异无统计学意义(P>0.05)。

Aim: To study the effect of active immunization with AT1 receptor peptides on hypertension development and cardiovascular remodeling in spontaneous hypertension rats (SHR). Methods: SHR were randomly allocated into 5 groups,among which 3 groups were actively immunized with ATR12181, ATR12185, and ATR10014, respectively, and the other 2 groups were treated with losartan and immune adjuvant(control), respectively; Wistar rats were allocated into 4 groups,among which,1 group was given immune adjuvant,and the other 3 groups were actively immunized with ATR12181,ATR12185,and ATR10014,respectively. The specific antibodies were detected by ELISA and blood pressure was measured by the tail-cuff method. The level of heart hypertrophy was assessed by the ratio of heart weight to body weight and the ratio of left ventricular weight to body weight. Results: The corresponding antibody had been found in all the animals immunized against ATR12181, ATR12185 and ATR10014. The systolic BP of SHR immunized with ATR12181 began to decrease after 1 month,which was significantly lower than that of SHR control group and had no significant difference compared with losartan group.The systolic BP of SHR immunized with ATR12185 or ATR10014 did not change obviously.Compared with SHR control group,the ratio of heart weight to body weight((14.66±0.50) mg/g vs (5.16±0.11) mg/g) and the ratio of left ventricular weight to body weight ((3.64±0.45) mg/g vs (4.19±0.07) mg/g) in SHR immunized with ATR12181 were reduced (P<0.05);the correspending antibodies was found in Wistar rats immunized with the 3 peptides. The systolic BP did not change obviously and no remarkable pathological changes of the hearts were observed.Conclusion: It is indicated that long-term immunized with ATR12181 can effectively reduce BP in SHR, attenuate and regress the heart hypertrophy.