高盐上调压力超负荷大鼠的脑内APJ受体表达  

Upregulation of brain APJ receptor expression induced by high salt in pressure overload rats

作　　者：张琪 谭颖颖[2] 刘东敏[2] 赵小明 

机构地区：[1]陕西中医学院医学科研实验中心,陕西咸阳712046 [2]陕西中医学院第一临床医学院,陕西咸阳712046

出　　处：《中国药理学通报》2015年第5期630-635,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31171101;81100175;81470543);教育部科学技术研究重点项目(No 212173);陕西省教育厅科学研究计划项目(No 2013JK0819;2013JK0763)

摘　　要：目的观察高盐对压力超负荷大鼠的交感神经活性和脑内Apelin和APJ系统的影响。方法♂SD大鼠,在肾动脉分支上方部分结扎腹主动脉,建立主动脉缩窄大鼠模型。术后4周,分别给予含8%Na Cl的高盐饲料或含0.3%Na Cl的常规饲料,喂养1周后,记录各组大鼠的血流动力学变化;ELISA分析24 h尿去甲肾上腺素(NE)水平;real-time RCR和Western blot方法观察室旁核Apelin和APJ的表达变化。另一组实验中,在给予高盐饲料的同时使用Alzet微渗透泵侧脑室灌流ML221或benzamil,观察24 h尿NE水平和心脏指数(HW/BW)变化。此外,在正常SD大鼠侧脑室灌流高钠脑脊液1周后,观察大鼠血压、24 h尿NE和APJ表达水平的变化。结果压力超负荷大鼠给予高盐饮食1周后,平均动脉血压(MAP)、心率(HR)、左室收缩末期压(LVESP)和24 h尿NE水平,以及室旁核的APJ mRNA和蛋白表达均较对照明显增加(P<0.05);而假手术组大鼠在进食高盐饲料后,血流动力学、24 h尿NE水平和APJ表达均未见明显改变。在侧脑室分别灌注APJ受体拮抗剂ML221或ENa C拮抗剂benzamil后,可以明显抑制高盐引发的压力超负荷大鼠24h尿NE水平和HW/BW比值变化(P<0.01)。在正常血压大鼠侧脑室灌注高Na+脑脊液1周后,也可出现脑内APJ表达上调以及MAP、HR和尿NE水平升高(P<0.01)。结论高盐可以增加压力超负荷大鼠模型的交感神经活性,而该效应与脑内的APJ受体表达上调和Na+敏感性增加密切相关。APJ受体可能是脑内盐敏感性形成的重要调控靶点。Aim To observe the effect of high salt stress on sympathetic nerve activity and brain Apelin and APJ system in pressure overload rats.Methods The suprarenal abdominal aorta was banded in male SD rats to create the pressure overload model.Four weeks later,the rats were fed a high-salt （8%NaCl）diet or a regular-salt （0.3% NaCl）diet for 1 week,and the hemodynamic changes of the rats were recorded.Sym-pathetic activity was evaluated by measuring 24 h uri-nary norepinephrine （NE）by ELISA.Real-time RCR and Western blot method were used to analyze the Ape-lin and APJ expression in the paraventricular nucleus of rats.In another protocol,ML22 1 or benzamil was intracerebroventricularly infused in the aorta banding rats fed with high-salt,and levels of 24 h urinary NE and cardiac index were recorded.In addition,normal SD rats were intracerebroventricularly infused with Na＋-rich aCSF for 1 week,and the changes of blood pressure,24 h urine-NE and APJ expression levels were detected.Results In the pressure overload rats fed with high salt diet for 1 week,the mean arterial blood pressure （MAP）,heart rate （HR）,left ventric-ular end systolic pressure （LVESP）,24 h urinary NE and APJ mRNA protein expression in paraventricular nuclear were significantly increased compared with those in control groups （P〈0.05 ）.However,the he-modynamics,24 h urinary NE and APJ expression showed no significant change in the sham rats fed a high salt diet.In addition,ICV infusion of APJ recep-tor antagonist ML221 or the ENaC antagonist benzamil significantly inhibited the 24 h urinary NE level and HW/BW ratio in the pressure overload rats fed high salt diet （P 〈0.01 ）.Intracerebroventricular infusion of high Na＋aCSF for 1 week in normotensive rats also significantly increased the MAP,HR,urinary-NE lev-els and brain APJ expression （P 〈0.0 1 ）.Conclu-sions High salt increases the sympathetic nerve activ-ity in rats with pressure overload model, which is closely related to the brain APJ receptor expression an

关 键 词：APELIN APJ受体 高血压 交感神经 主动脉缩窄 盐敏感性 

分 类 号：R-332[医药卫生] R322.81