α7-nAChR介导的小花棘豆臭豆碱对小鼠海马组织谷氨酸代谢的调控机制

Study on α7-nAChR mediated glutamate metabolic mechanism of rat hippocampus by theanagirine of O.glabra DC

臭豆碱是小花棘豆的主要有毒成分之一,本试验目的是证明臭豆碱通过作用α7烟碱乙酰胆碱受体(α7-nAChR)调控谷氨酸代谢的毒理作用。结果显示,9 mg/kg和18 mg/kg臭豆碱口服剂量可激动小鼠海马组织α7-nAChR,促进谷氨酸释放及上调谷氨酸/天冬氨酸转运体(GLAST)表达,该效应可被α7-nAChR抗激动剂MLA抑制。但是,36 mg/kg臭豆碱口服剂量却增加小鼠海马谷氨酸浓度及下调GLAST表达。结果表明,超过36 mg/kg臭豆碱剂量则通过抑制α7-nAChR降低GLAST表达,导致谷氨酸代谢障碍从而具有潜在的谷氨酸神经毒性。

Anagirine is recognized as a toxic ingredient of Oxytropis glabra(Lam.)DC.This study was to test the hypothesis that anagirine could mediate glutamate metabolism throughα7 nicotinic acetylcholine receptor(α7-nAChR).In this work,we demonstrated that anagirine promoted the glutamate release and GLAST expression in rat hippocampus by activatedα7-nAChR in doses of 9 mg/kg and 18 mg/kg orally,while these effects were blocked by theα7-nAChR antagonist,MLA.However,anagirine increased the glutamate level and down-regulated GLAST expression in dose of 36 mg/kg orally.These results showed that anagyrine of Oxytropis glabra DC could act as an agonist or a desensitizer ofα7-nAChRs,depending on its doses,and it has potential glutamate neurotoxicity over 36 mg/kg by inhibitedα7-nAChRs in ICR mice.