血管紧张素Ⅱ1型受体在肥胖相关性高血压大鼠肾脏的表达及功能  

Expression and function of angiotensinⅡtype 1 receptor in the kidney of obesity-related hypertensive rats

作　　者：罗浩[1] 王新全[1] 王甲良[1] 陈硕[1] 陈彩宇[1] 曾春雨[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：《中华高血压杂志》2014年第7期666-670,共5页Chinese Journal of Hypertension

基　　金：国家自然科学基金(31130029、30925018)资助

摘　　要：目的探讨肥胖Zucker大鼠肾脏血管紧张素Ⅱ1型受体(AT1R)在肥胖相关性高血压发生机制中的可能作用。方法选12周龄的雄性瘦型及肥胖型Zucker大鼠,血糖仪测定血糖,酶联免疫吸附试验(ELISA)法测定血清胰岛素,血生化仪测定血清三酰甘油及总胆固醇,无创鼠尾测压仪测量血压,代谢笼测定24h尿。肾上腺动脉灌注AT1R拮抗剂(坎地沙坦)后测定尿钠排泄。实时荧光定量聚合酶链反应(qRT-PCR)检测大鼠肾脏AT1R的mRNA表达,Western blot测定大鼠肾脏AT1R蛋白表达。结果肥胖Zucker大鼠一般生理指标,包括体质量、肾脏大小、空腹血糖、胰岛素、三酰甘油及总胆固醇较瘦型Zucker大鼠升高(均P<0.05)。24h尿液分析,肥胖Zucker大鼠的基础尿量及尿钠排泄率明显高于瘦型大鼠[尿量:(6.84±0.75)比(4.36±0.55)mL,尿钠排泄率:(189.9±23.4)比(148.8±15.4)μmol/d;P<0.05],但校正体质量后,基础尿量及尿钠排泄率低于瘦型对照大鼠[单位体质量尿量:(14.42±1.12)比(17.49±1.59)mL/(d·kg);单位体质量尿钠排泄率:(454.7±52.5)比(598.4±61.9)μmol/(d·kg);P<0.05]。肾上腺动脉灌注AT1R拮抗剂后,肥胖Zucker大鼠的排钠利尿作用高于瘦型大鼠(P<0.05)。同时肥胖Zucker大鼠肾脏AT1R的mRNA及蛋白表达也高于瘦型大鼠。结论肥胖Zucker大鼠对坎地沙坦有明显的排钠利尿反应。Objective To study the role of renal angiotensin Ⅱ type-1 receptor （AT1R） in the pathogenesis of obesi- ty-related hypertension. Methods 12 week-old male lean or obese Zucker rats were used; blood glucose, serum to- tal cholesterol, triglyceride and insulin were determined. Blood pressure was measured with noninvasive tail cuff method. 24-hour urine flow and sodium excretion were examined by stainless steel metabolic cages. Urinary sodi- um excretion was determined after suprarenal artery candesartan infusion. The mRNA and protein levels of renal AT1R were quantified by quantitative real-time polymerase chain reaction（qRT-PCR） and Western blot. Results Compared with lean rats, obese rats exhibited higher body weight and kidney weight; higher levels of blood glucose, serum total cholesterol, triglyceride as well as insulin. In 24-hour urine analysis, the basic urine flow and urinary sodium excretion rate was significantly higher in obese rats than lean rats[urine volume （6. 844±0.75） vs {4.36± 0.55 ） mL, urinary sodium（ 189.9± 23.4 ） vs （ 148.8 ± 15.4 ）/μmol/d; all P〈0.057, however, after adjusted for body weight, it became significantly lower in obese rats than lean rats [urine volume adjusted for body mass （14.42 ± 1.12） vs （ 17.49 ± 1.59/mL/d · kg）; urinary sodium adjusted for body mass （ 454.7 ± 52.5 ） vs （ 598.4 ± 61.9）/Lmol/（d · kg） ;all P〈0.05]. Compared with lean rats, obese rats possessed stronger effect in candesartan induced natriuresis and diuresis and their kidney AT1R mRNA and protein expressions were also higher. Conclusion Compared with lean Zucker rats, obese Zucker rats possess a stronger effect of the AT1R antagonist candesartan on natriuresis and diuresis.

关 键 词：血管紧张素Ⅱ1型受体 肥胖相关性高血压 Zucker大鼠 

分 类 号：R544.1[医药卫生—心血管疾病]