胃动素受体激动剂红霉素对大鼠下丘脑葡萄糖反应神经元的作用

EFFECT OF MOTILIN RECEPTOR AGONIST-ERYTHROMYCIN ON THE GLUCORESPONSIVE NEURONS IN HYPOTHALAMUS OF RATS

目的:通过观察胃动素受体激动剂红霉素对大鼠下丘脑中葡萄糖反应神经元电活动的影响,探讨中枢胃动素对摄食活动调控的机制。方法:应用细胞外记录神经元单位放电的方法,记录麻醉大鼠LHA及VMH的神经元电活动。左颈总动脉注射0.56mol/L葡萄糖溶液0.2ml鉴别GSNs及GRNs;侧脑室注射红霉素4μg,观察其对葡萄糖反应神经元及非葡萄糖反应神经元自发放电频率的影响;侧脑室注射GM-109(胃动素受体拮抗剂)与红霉素的混合剂(1∶50的比例配制),观察上述效应是否可重复出现。结果:在LHA,红霉素对GSNs有明显的兴奋作用,与其对该核团NGSNs的作用相比较,差别有统计学意义(P<0.05);在VMH,红霉素对GRNs有明显的抑制作用,与其对该核团NGRNs的作用相比较,差别有统计学意义(P<0.01)。对红霉素有反应的神经元在给予GM-109和红霉素的混合剂后,神经元的放电频率无明显变化。结论:胃动素受体激动剂红霉素可兴奋LHA-GSNs同时抑制VMH-GRNs,这一途径可能是中枢胃动素促进摄食活动的神经调节机制之一。

Aim： In order to explore the mechanism of central motilin-induced feeding behavior, the effects of erythromycin, a motilin receptor agonist, on glucoresponsive neurons in hypothalamus were observed. Methods： Extracellular recordings were made from single neurons in region of lateral hypothalamic area（LHA） and ventromedial hypothalamic nucleus（VMH） in anesthetized rats. On the basis of their responsiveness to intracarotid injection of 0.58 mol/L glucose solution 0.2 ml, glucose-sensitive neurons（GSNs） in LHA and glucoreceptor neurons（GRNs） in VMH were recognized. Effects of intracerebroventricularly（i, c. v. ） administration of 4μg erythromycin on neural activities of glucoresponsive neurons and non-glucoresponsive neurons were examined. The mixture of EM and GM-109 1 μ1 were used to GSNs and GRNs which were sensitive to i. c. v. administration of EM. Results： In LHA, EM increased activity of GSNs significantly（P〈 0.05 vs non-glucose-sensitive neurons group）. Whereas in VMH, EM significantly decreased the activities of GRNs（P 〈 0.01 vs non-glucoreceptor neurons group）. The mixture of EM and GM-109 had no effect on GSNs and GRNs. Conclusion： EM, a motilin receptor agonist, can stimulate GSNs in LHA and suppress GRNs in VMH and this may contribute to central motilin＇s effect on feeding behavior.