侧脑室注射匹罗卡品引起内源性洋地黄素释放抑制肾皮质Na+_K+ATP.docVIP

侧脑室注射匹罗卡品引起内源性洋地黄素释放抑制肾皮质Na+_K+ATP 　【摘要】 目的：探讨激活SD大鼠脑内胆碱能M受体对内源性洋地黄素(EDLF)释放及肾皮质Na+_K+ATP酶活性的影响。方法：侧脑室注射M受体激动剂匹罗卡品，放射免疫法测定血清EDLF水平，化学比色法测定肾皮质Na+_K+ATP酶活性。结果：①侧脑室注射匹罗卡品引起大鼠血清EDLF水平显著升高(Plt;0.01)，肾皮质Na+_K+ATP酶活性抑制(Plt;0.01)。②侧脑室注射阿托品可阻断匹罗卡品引起的血清EDLF水平升高和肾皮质Na+_K+ATP酶活性抑制效应。结论：脑内胆碱能系统可通过M受体介导参与EDLF释放的调节。 【关键词】 M受体 匹罗卡品 阿托品 内源性洋地黄素 肾皮质Na+_K+ATP酶 　　［Abstract］Objective: To investigate the possible effect of pilocarpin microinjection into cerebroventricule on level of serum endogenous digitalis_like factor(EDLF)and activity of renal cortical Na+_K+ATPase in rats. Methods: After intracerebroventricular administration of pilocarpin(10 μg/rat), the serum EDLF level was determined with the radioimmunoassay and the activity of renal cortical Na+_K+ATPase was determined with chemical assay. Results: After intracerebroventricular injection of pilocarpin, the serum EDLF level was increased and the activity of renal cortical Na+_K+ATPase was decreased obviously, which could be blocked by administration of M_receptor antagonist atropine(20 μg). Conclusion: The intracerebroventricular microinjection of pilocarpin can increase EDLF release mediated by central muscarinic receptor. 　　［Key Words］M receptor；pilocarpin；atropine；endogenous digitalis_like factor；renal cortical Na+_K+ATPase 　　脑内胆碱能系统与机体钠水排出的调节有密切关系，在侧脑室、第三脑室或下丘脑外侧等部位分别注射胆碱能受体激动剂氨甲酰胆碱可引起排钠、排钾和利尿反应,这种效应可被M受体阻断剂和N受体阻断剂阻断［1，3］。内源性洋地黄素(Endogenous digitalis_like factor, EDLF)是来自下丘脑和肾上腺、通过抑制Na+_K+ATP酶活性而发挥排钠利尿、强心和缩血管等作用的生物活性物质［2］。脑内胆碱能刺激的排钠利尿效应是否与EDLF释放有关尚未见报道。本实验通过选择性激活脑内胆碱能M受体，观察血清EDLF水平及肾皮质Na+_K+ATP酶活性的变化，试图就脑内胆碱能M受体对EDLF的释放及肾皮质Na+_K+ATP酶活性的影响进行探讨。 　　1 方法 　　1.1 实验动物与分组 　　实验用SD大鼠(第三军医大学实验动物中心提供)27只，体质量180～250g，雌雄不拘，并随机分为人工脑脊液组(7只,侧脑室注射人工脑脊液5μL)、匹罗卡品组(7只,侧脑室注射匹罗卡品10μg)、人工脑脊液预处理组(7只,侧脑室注射5μL人工脑脊液10min后再注射匹罗卡品10μg)和阿托品预处理组(6只,侧脑室注射阿托品20μg预处理10min后再注射匹罗卡品10μg)。乌拉坦(1g/kg)腹腔注射麻醉后，埋植侧脑室导管(AP 5mm，L 1.5mm，深度3.5mm)。注射药物均用人工脑脊液稀释(NaCl 7.46g，KCl 0.19g，CaCl2 0.14g，MgCl2 0.19g稀释至1000mL)。侧脑室注射后30min分别取动脉血和肾皮质用于测定血清EDLF水平和肾皮质Na+_K+ATP酶活性。 　　1.