谷氨酸单钠对成年小鼠的神经毒性作用  

Neurotoxic effects of monosodium glutamate in adult mice

作　　者：高静[1] 吴娟[1] 林凌[1] 柳祎 赵晓宁[1] 张祖暄[1] 

机构地区：[1]南京大学医学院神经生理教研室

出　　处：《中国药理学与毒理学杂志》1994年第4期276-280,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：江苏省自然科学基金;南京大学现代分析中心测试基金

摘　　要：［３Ｈ］谷氨酸（Ｃｌｕ）ｓｃ后的不同时程，柱层析分离血清中［３Ｈ］Ｇｌｕ，液闪测定，发现随代谢时程的延长［３Ｈ］Ｇｌｕ的量明显降低。外周组织中［３Ｈ］Ｇｌｕ含量的变化与血清中的类似，而神经组织则不同。非标记谷氨酸单钠ｓｃ以剂量依赖方式损伤成年小鼠的分辨学习能力。引起特征性神经元退变，降低下丘脑和脊髓的线粒体膜结合钙水平。结果表明，４．０ｍｇ·ｇ－１谷氨酸单钠可以透过血脑屏障对成年动物产生神经毒性作用。其作用机理可能与细胞内Ｃａ２＋超载，线粒体封存或排空Ｃａ２＋的能力失常。最终导致神经元损伤甚至死亡有关。Radioactivity of[3H]glutamic acid(Glu),separated by Sephadex G-50 chromatographyfrom serum of adult mice, subcutaneously injectedwith 2.5 mg·g-1 monosodium glutamate(MSG)con-taining[3H]Glu(640 kBq),was detern1ined by liquidscintillation counting at 10,30 and 60 min after thedrug administration. Remarkable decrease wasappeared at 30 and 60 min in comparison with 10 and30 min respectively. Similar changes in radioactivityalso occurred in peripheral tissues, such as liver andkidney,but differently in nervous svstem includingforebrain, cerebellum and spinal cord,which indicatedthat exogeneous Glu could penetrate blood-brainbarrier. Neurotoxic effects of MSG were proved in theadult mice treated with higher(4.0 mg·g-1 )and lower(2.5 mg·g-1)doses of MSG. In Y-maze behavioraltraining,the discrimination learning abilities weresignificantly affected in a dosc-dependent fashion.while one-trial passive avoidance behavior and painthreshold were ignored.Meanwhile, characteristicneuronal injuries occurred in not onIv arcuate nucleusof hypothalamus but also ventromedial nucleus andmedian eminence, especially in the group treated withhigher dose of MSG。Similar dose-dependent altera-tions also appeared in mitochondrial membrane boundCa2+,detected by Tb3+ fluorescent probe. Followingthe treatment of higher dose of MSG,Tb3+ fluorescentintensity in hypothalamus and spinal cord wasincreased from 29±s 3 and 31±s lto 34 ±s 4 and 34±s 2 respectively,i.e. that intensity in mitochondrialmembrane bound Ca2+was decreased significantly.These findings further indicated that MSC could insultadult animal through blood-brain barrier,and suggestthat the mechanisms underlyingthe neurotoxic effectsof MSG may be associated with the overloading ofintracellular Ca2+,the dysfunction of mitochondrion todeplete or sequester Ca2+, as well as the irreversibleneuronal injurv and death in relative brain regions.

关 键 词：谷氨酸钠 血脑屏障 下丘脑 神经毒性 毒理学 

分 类 号：R992[医药卫生—毒理学]