肥胖性高血压大鼠肾脏瘦素受体及水通道蛋白2的表达

摘要

目的：观察肥胖性高血压大鼠（OHR）肾脏瘦素（Lep）受体（LepR）与水通道蛋白2（AQP2）表达的情况，探讨OHR Lep抵抗机制及肾在高Lep血症作用下的病理改变。方法由高脂饮食诱导建立OHR模型，与自发性高血压大鼠（ SHR）和正常Wistar大鼠对照。应用酶联免疫吸附法（ ELISA）检测大鼠血清中甘油三酯（ TG）、总胆固醇（TC）、Lep、血管加压素（AVP）、血管紧张素Ⅱ（AngⅡ）、β2微球蛋白（β2-MG）变化，光镜下观察肾组织的形态结构，实时荧光定量PCR检测肾LepR与AQP2的mRNA表达，蛋白免疫印迹法检测相关蛋白表达情况。结果与正常对照组比较，模型组大鼠血中TG、TC、Lep、AVP、AngⅡ、β2-MG均明显升高（P＜0．05），大鼠肾LepR、AQP2的mRNA表达上调（P＜0．05）。与SHR组比较，大鼠血清中TG、TC、Lep升高。模型组大鼠血清中Lep与血清中β2-MG、AVP呈线性相关（R2＝0．87；R2＝0．95）。结论肾参与OHR水代谢紊乱和Lep抵抗的病理过程，可能是肥胖导致高血压的重要机制之一。%Objective To observe the expression of leptin(Lep) receptor (LepR) and aquaporin 2 (AQP2) in the kidneys of obesity-related hypertensive rats ( OHR ) and to explore the mechanism of Lep resistance and water metabolic disorders in them.Methods OHR( model group) were induced by high-fat diet.Normal Wistar rats were chosen as normal control and hypertensive rats(SHR) as positive control.The serum level of triglycerides(TG), total cholesterol(TC), Lep, vasopressin ( AVP ) , angiotensinⅡ( AngⅡ) and β2-microglobulin (β2-MG ) was measured by enzyme linked immunosorbent assays ( ELISA) and renal morphology was observed by HE staining.The density of LepR and AngⅡtype 1( AT1) in the kidney was observed by immunohistochemistry.mRNA And protein expression of LepR and AQP2 in the kidney was assayed by real-time polymerase chain reaction and Western blotting.Results Compared with normal rats,the TG, TC, Lep, AVP, AngⅡand β2-MG of the model group were significantly increased (P<0.05), and protein and mRNA expression of LepR and AQP2 in the kidney were up-regulated (P<0.05).Compared with SHR group, TG, TC and Lep in serum of the model group were significantly increased (P<0.05).The concentrations of AVP,β2-MG and Lep was linearly related(R2 =0.87,R2 =0.95).Conclusion Water metabolic disorder and Lep resistance may be involved in the kidney injury of OHR, which may be one of the important pathogeneses of obesity-related hypertension.