β1受体反义基因对肾性高血压大鼠心脏β受体的影响  

Effects ofβ1 adrenoceptor antisense on blood pressure andβ1 adrenoceptor mRNA and protein in renal hypertension rats

作　　者：梁远红[1] 林曙光[1] 周燕[2] 王晋明[3] 王芳[3] 余细勇[1] 

机构地区：[1]广东省心血管病研究所,广州510100 [2]武汉大学人民医院急诊科 [3]武汉大学人民医院心内科

出　　处：《中华急诊医学杂志》2007年第11期1151-1154,共4页Chinese Journal of Emergency Medicine

基　　金：中国博士后科学基金(20060400780);广东省医学科研基金(A2007022);广东省自然科学基金(7001120)

摘　　要：目的观察阳离子脂质体混合物与β1受体反义寡核苷酸(β1-AS-ODN)单次注射对两肾一夹肾性高血压大鼠血压及心脏β受体mRNA、受体密度的影响。方法用SD大鼠制作两肾一夹肾性高血压模型,将动物随机分为5组,每组18只:β1-AS-ODN组,β1-IN-ODN组,2KIC组,假手术组,SD组。于术后第4周经鼠尾静脉注射阳离子脂质体/β1-ODN的混合物(摩尔比2.0),注射剂量为0.5mg·kg^(-1),Tail-cuff法检测血压,半定量RT-PCR测定β1mRNA水平,放射免疫法测定受体密度,Western blot测定蛋白水平。数据采用one-way ANOVA分析,两两比较用Newman-Keuls法。结果与2KIC组相比,β1-AS-ODN可使血压下降维持4周(P<0.05),可以使血压最大下降39 mmHg;β1-AS-ODN组与高血压组β1受体mRNA水平无明显差异,但β1受体蛋白水平明显降低(P<0.05);与2K1C组比较,注射后第2、7、30天反义组的β1受体水平明显降低,分别为29.5%、35.5%、20.4%(P<0.01,P<0.01,P<0.05);三组β2受体水平差异无统计学意义。结论以β1受体为靶基因的反义基因治疗降压效果显著,β1反义寡核苷酸在转录后发挥作用抑制目的基因表达;β1反义寡核苷酸的降压效果与其特异性地和心脏β1受体结合相关,而与β2受体无关。Objective To evaluate the effects of β1 adrenoceptor antisense on blood pressure and β1 adrenoceptor mRNA and protein levels in 2 kidney 1 clip （2K1C） rats. Method 2K1C hypertensive rats were produced by clipping renal artery of SD rats. Liposome/AS-ODNs 2.0 were tested intravenously in rats with 2K1C hypertension. Animals were divided into 5 groups （n = 18 in each group）： β1-AS-ODN group, β1-IN-ODN group, 2K1C group, Sham group and SD group. Blood pressure was measured by tail-cuff method, the levels of myocardial β adrenoceptor mRNA and protein were tested by RT-PCR and binding assay. Results On the basis of the magnitude and duration of hypotension, β1-AS-ODN decreased blood pressure by 39 mmHg at the most for 4 weeks. Compared with the 2K1C group, β1-AS-ODN did not significantly change the levels of myocardial β1 adrenoceptor mRNA but significantly decreased the levels of myocardial β1 adrenoceptor protein at 2, 7, 30 days （P 〈 0.01, P 〈 0.01, P 〈 0.05; respectively）. Conclusions β1-AS-ODN can significantly decrease blood pressure in 2K1C hypertensive rats, which is associated with reducing the levels of myocardial β1 adrenoceptor protein. The inhibition of β1-AR expression probably occurs during post-transcriptional steps.

关 键 词：Β1受体 两肾一夹肾性高血压 反义寡核苷酸 

分 类 号：R544.1[医药卫生—心血管疾病]