不同位置肾素血管紧张素醛固酮系统阻断剂对肾血管性高血压大鼠血浆血管紧张素Ⅱ1型受体及其抗体的影响

Influence of different inhibitors of renin-angiotensin-aldosterone systems on peripheral angiotensin Ⅱ type 1 receptor and its antibodies in renovascular hypertension rats

目的观察佐芬普利、奥美沙坦、依普利酮对肾性高血压大鼠血压、心肌肥厚及外周血血管紧张素Ⅱ1型受体(AT1R)及其抗体(AT1R-Ab)的影响。方法 120只清洁型雄性SD大鼠随机分为假手术组、两肾一夹组、两肾一夹+佐芬普利组(Z)、两肾一夹+奥美沙坦组(O)和两肾一夹+依普利酮组(E),每组24只。对后4组以两肾一夹制作肾血管性高血压模型。制模4周后,药物干预组分别采用佐芬普利10mg/kg、奥美沙坦3mg/kg、依普利酮100mg/kg灌胃,假手术组、两肾一夹组以等体积蒸馏水灌胃。术后8、12、14周,超声心动图观察心脏结构和功能,每组处死6只大鼠取主动脉血;采用酶联免疫吸附技术(ELISA)检测血浆AT1R、AT1R-Ab水平。结果术后8周,假手术组、两肾一夹组的AT1R水平差异无统计学意义(P>0.05);各干预组AT1R水平较两肾一夹组上升(均P<0.05)。术后12周、14周两肾一夹组大鼠动脉血浆AT1R水平较同期假手术组上调;Z、E干预组AT1R水平较两肾一夹组升高[12周:(74.63±0.83)、(75.85±3.09)比(67.56±1.67)ng/L;14周:(78.29±0.31)、(78.05±1.12)比(73.90±1.98)ng/L,均P<0.05];而O组与两肾一夹组差异无统计学意义(P>0.05)。术后8周,两肾一夹组大鼠血浆AT1R-Ab水平较假手术组升高;术后12、14周两肾一夹组大鼠血浆AT1R-Ab水平较术后8周降低;各时段Z、E组AT1R-Ab水平均较两肾一夹组降低[8周(2.10±0.10)、(2.13±0.18)比(2.75±0.13)ng/L,12周(2.00±0.10)、(2.03±0.1)比(2.32±0.10)ng/L;14周(1.99±0.16)、(2.00±0.09)比(2.23±0.23)ng/L;均P<0.05];而O组与两肾一夹组差异无统计学意义(P>0.05)。结论肾性高血压大鼠血压、血浆AT1R、AT1-Ab水平随时间动态变化。奥美沙坦、佐芬普利、依普利酮降低大鼠血压、减小心肌肥厚程度、上调动脉血AT1R水平;佐芬普利、依普利酮下调动脉血浆AT1R-Ab水平,而奥美沙坦对AT1R-Ab无明显影响。

Objective To investigate the effects of olmesartan, zofenopril and eplerenone on angiotensin Ⅱ type t receptor （AT1 R） and antibody against AT1R （AT1R-Ab） in two-kidney one clip （2K1C） renovascular hypertensive rats. Methods One hundred and twenty male Sprague-Dawly rats were randomly divided into Sham, 2K1C, 2KIC＋ olmesartan（O）, 2K1C＋zofenopril（Z） and 2K1C＋eplerenone group（E）, with 24 rats in each group. 2K1C hyper- tensive model was established in the last four groups, Four weeks after operation, rats in O, Z and E group were treated with olmesartan （3 mg/kg）, zofenopril （10 mg/kg） and eplerenone（100 mg/kg） by garage respectively, while rats in Sham and 2K1C group were treated with equal volume distilled water. The myocardial structure and function were detected by ultrasonography, and the plasma AT1 R, ATIR-Ab were evaluated by ELISA at 8, 12 and 14 weeks after operation. Results At 8 weeks after operation, the level of plasma AT1R in 2K1C group wasnot significantly different from that in sham group, while it was increased in O, Z and E groups （all P〈0.05）. At 12 or 14 weeks after operation, the level of plasma AT1R in 2K1C group was higher than that in sham group and lower than that inZandE groups [12 week （67.564±1.67） vs （74.63±0.83）, （75.85±3.09） ng/L; 14 week （73.90±1.98） vs （78.29±0.31）, （78. 05±1.12）ng/L, respectively, all P〈0.05-1. While, there was no signifi- cant difference between 2K1C group and O group in plasma AT1R levels. Compared with sham group, plasma AT1R-Ab levels in 2K1C group were higher at 8 weeks after operation, which was decreased at 12 and 14 weeks. The levels of plasma AT1R-Ab in Z and E groups were lower than that in 2K1C group at each time points [8 week （2. 10±0.10）,（2.13±0.18）vs（2.75±0.13）ng/L; 12 week（2.00±0.10）,（2.03±0.1）vs（2.32±0.10_ng/L; 14 week（1. 99±0. 16）, （2.00±0.09）vs（2. 23±0.23）ng/L; all P〈0.05]/ While, there was no significant differ ence between 2K1C group and O group in plasma AT1R-Ab levels. Conclusion Plasma levels of AT1R, AT1R- Ab, and blood pressure were always changing with time in renovascular hypertensive rats. Olmesartan, zofenopril and eplerenone decreased blood pressure and the thickness of left ventricle, but up regulated the plasma AT1R. Zofenopril and eplerenone but not olmesartan reduced the levels of AT1R-Ab.