β_1肾上腺受体反义基因对高血压大鼠前肾素、血管紧张素Ⅱ的影响  

Effects of β_1 Adrenoceptor Antisense on Blood Pressure, Preprorenin mRNA and Plasma Ang Ⅱ in Hypertensive Rats

作　　者：梁远红[1] 林曙光[1] 周燕[2] 王晋明[2] 王芳[2] 余细勇[1] 

机构地区：[1]广东省人民医院医学研究中心,广东省心血管病研究所,广东广州510100 [2]武汉大学人民医院,湖北武汉430060

出　　处：《中华高血压杂志》2007年第6期481-484,共4页Chinese Journal of Hypertension

基　　金：湖北省自然科学基金资助项目(2004AA309B09);国家自然科学基金项目(30300421)

摘　　要：目的观察β1肾上腺受体反义基因对肾性高血压大鼠血压、前肾素原 mRNA和血浆血管紧张素Ⅱ(AngⅡ)的影响,探讨基因治疗降低血压的机制。方法制作两肾一夹肾性高血压模型,阳离子脂质体与β1反义寡核苷酸经鼠尾静脉注射。共聚焦检测荧光,鼠尾袖带法(tail-cuff法)测血压,半定量RT-PCR测定前肾素原 mRNA水平,放免法测定血浆AngⅡ水平。结果β1反义寡核苷酸可使血压下降维持4周,血压最大下降39mmHg;与高血压组比较,注射后第7天反义组的前肾素原 mRNA、AngⅡ水平无统计学意义;注射后第28天,反义组的前肾素原 mRNA、AngⅡ水平降低差异有统计学意义(P<0.05,P<0.01)。结论以β1肾上腺受体为靶基因的反义基因治疗降压效果显著,其机制是先作用于交感神经系统再作用于肾素血管紧张素系统来发挥作用。Objective To evaluate the effects of β1 adrenoceptor antisense on blood pressure, preprorenin mRNA and plasma Ang Ⅱ in Goldblatt hypertensive rats. Methods liposome/AS-ODNs（molar ratio 2. 0）were administered intravenously in rats with 2 kidney 1 clip （2K1C） hypertension, Blood pressure was measured by tail-cuff method, the levels of preprorenin mRNA were assessed by RT-PCR; and plasma Ang Ⅱ were examined by radioimmunoassay. Results β1-AS-ODN decreased blood pressure in hypertensive rats maximal to 39 mm Hg and remained for 4 weeks. Compared with the 2K1C group, the levels of preprorenin mRNA and plasma Ang Ⅱ were not changed on day 7 by AS-ODN treatment. However, the levels of preprorenin mRNA and plasma Ang Ⅱ was significantly reduced by AS-ODN treatment on day 28 （P〈0.05, P〈0.01）. Conehtsion β1-AS-ODN significantly decreased blood pressure in 2K1C hypertensive rats which was associated with primary attenuation of the levels of renal β1 adrenoceptor protein and secondary inhibition of renin-angiotensin system.

关 键 词：β1肾上腺受体 基因治疗 两肾-夹高血压 血管紧张素Ⅱ 

分 类 号：R544.1[医药卫生—心血管疾病]