G蛋白偶联受体激酶4对内皮素B型受体的异常调节在原发性高血压发生中的作用  

Role of G protein coupled receptor kinase 4 in regulation of renal endothelin receptor B in essential hypertension rats

作　　者：李美香[1] 郑硕[1] 姚勇刚[1] 陈彩宇[1] 任红梅[1] 曾春雨[1] 周林[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所心血管内科,重庆市心血管病研究所,重庆400042

出　　处：《第三军医大学学报》2015年第3期243-247,共5页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81070559)~~

摘　　要：目的探讨G蛋白偶联受体激酶4（G protein-coupled receptor kinase 4,GRK4）对内皮素B型受体（endothelin receptor B,ETB）的异常调节在原发性高血压中的作用及机制。方法选用12～14周龄,体质量300 g左右的雄性自发性高血压大鼠（spontaneously hypertensive rats,SHRs）及其对照鼠（Wistar-Kyoto,WKY）各10只,通过无创鼠尾测压仪测定血压,采用右肾上腺静脉插管灌注ETB受体特异性激动剂BQ3020后观察尿流速及尿钠排泄率,荧光定量PCR检测大鼠肾脏GRK4 mRNA水平,Western blot测定大鼠肾脏GRK4及ETB受体的蛋白表达差异,免疫共沉淀法检测ETB受体磷酸化情况,在动物水平观察高血压状态下ETB受体的功能情况。结果 ETB受体激动剂BQ3020对WKY大鼠有明显利尿排钠作用,且这种利尿排钠作用可以被ETB受体抑制剂BQ788阻断,但在SHR大鼠BQ3020的利尿排钠作用受损[尿流速：（11.23±2.16）vs（3.49±1.32）,P〈0.05];尿钠排泄率：[（1 551.43±393.47）vs（601.16±128.15）,P〈0.05];在SHR大鼠肾皮质GRK4的蛋白水平及mRNA水平均较WKY大鼠高[蛋白：（1.38±0.10）vs（0.85±0.07）,P〈0.05];mRNA：[（2.23±0.15）vs（0.78±0.16）,P〈0.05],SHR大鼠ETB受体总蛋白水平与WKY大鼠相比差异无统计学意义（P〉0.05）,但ETB受体磷酸化水平增高。结论 GRK4可能通过对内皮素B型受体的异常调节,参与了原发性高血压发生与发病。Objective To determine the effect of G protein coupled receptor kinase 4（ GRK4） on the regulation of renal endothelin receptor type B（ ETB） and investigate its role in the pathogenesis of essential hypertension. Methods Spontaneously hypertensive rats（ SHRs） and Wistar-Kyoto（ WKY） rats（ male,12 weeks old,and weighting about 300 g） were subjected in this study（ n = 10 for each group）.Blood pressure（ BP） was detected by using a noninvasive tail-cuff method. Then ETB antagonist,BQ3020,was perfused through suprarenal artery administration,the natriuresis and diuresis were determined in SHRs and WKY rats. The mRNA levels of GRK4 in the renal tissue was measured by qRT-PCR. The protein levels of renal GRK4 and ETB were detected by Western blotting. The serine phosphorylation level of ETB was measured by co-immunoprecipitation. Results ETB agonist BQ3020 resulted in significant increases in the diuresis and natriuresis in WKY rats,which were impaired in SHRs（ urine flow： 11. 23 ± 2. 16 vs 3. 49 ±1. 32,P〈0. 05; urine sodium excretion： 1 551. 43 ± 393. 47 vs 601. 16 ± 128. 15,P〈0. 05）. The GRK4 expression was obviously higher in the renal cortex from SHRs than from WKY rats（ protein expression：1. 38 ± 0. 10 vs 0. 85 ± 0. 07,P〈0. 05; mRNA： 2. 23 ± 0. 15 vs 0. 78 ± 0. 16,P〈0. 05）. Though there was no significant difference in renal ETB pretein level between SHRs and WKY rats,the serine phosphorylation level of ETBR was higher in SHRs than WKY rats. Conclusion GRK4 participates in the pathogenesis and development of essential hypertension,probably via regulating renal ETB.

关 键 词：内皮素B型受体 G蛋白偶联受体激酶4 尿钠排泄 原发性高血压 

分 类 号：R345.57[医药卫生—基础医学] R363.21