脑损伤后N-乙酰天冬氨酰谷氨酸肽酶抑制的神经保护  

Neuroprotective effects of NAAG peptidase inhibition on the treatment of traumatic brain injury

作　　者：钟春龙[1] 江基尧[1] 罗其中[1] 赵学仁[2] Bruce G.Lyeth 

机构地区：[1]上海交通大学医学院附属仁济医院神经外科,200127 [2]美围加利福尼亚大学戴维斯分校神经外科

出　　处：《中华神经外科杂志》2009年第10期937-940,共4页Chinese Journal of Neurosurgery

基　　金：基金项目：国家自然科学基金（30500525,30670719）;上海市科委基金（07JC14038,09140901300）;上海市青年科技启明星计划（05QMX1428）资助项目

摘　　要：目的探索颅脑损伤后N-乙酰天冬氨酰谷氨酸（NAAG）肽酶抑制的神经保护效应。方法将20只SD大鼠随机分成4组后制作中度液压颅脑损伤模型。伤后3个时间点（即时，8h，16h）分别经腹腔注射新型NAAG肽酶抑制剂ZJ-43（各组剂量：0，50，100，150mg／kg）。伤后24h处死动物取脑组织行Fluoro—Jade B组织荧光染色以及GFAP免疫组化染色。通过立体细胞计数着重观察大鼠海马CA2／3区退变神经元及正常胶质细胞的数量变化。结果，ZJ-43能显著减少颅脑损伤后的神经元退变（P〈0．01），其中小剂量处理组（50mg／kg）保护作用最佳，还能同时显著减少颅脑损伤后的胶质细胞丢失（P〈0.05）。结论阻断NAAG肽酶活性能有效放大内源性递质NAAG的神经保护作用，从而阻断谷氨酸兴奋毒性的病理进程，有望成为治疗颅脑损伤的新策略。Objective To explore the neuroprotective effects of NAAG peptidase inhibition on the treatment of traumatic brain injury. Method A total of 20 male Sprague - Dawley rats were divided into 4 groups, then sustained to moderate lateral fluid percussion TBI. A novel NAAG peptidase inhibitor, ZJ- 43, was used in 4 different doses （0, 50, 100, or 150 mg/kg）. Each dose was repeatedly administered i.p. （ n =5/group） by multiple injections at 3 times （0 h, 8 h, 16 h） after TBI. Rats were euthanized at 24 hrs after TBI and brains were processed and stained according to the Fluoro - Jade B Histofluoreseence and GFAP Immunohistochemistry protocols. Ipsilateral neuronal degeneration and bilateral astrocyte loss in the CA2/3 regions of the hippocampus were quantified using stereological techniques. Results Compared with vehicle, ZJ - 43 significantly reduced the number of the ipsilateral degenerating neurons （ P 〈 0. 01 ） with the greatest neuroprotection at the 50 mg/kg dose. Moreover, 50 mg/kg of ZJ -43 also significantly reduced the ipsilateral astrocyte loss （ P 〈 0. 05 ） . Conclusions Blockade of NAAG peptidases may augment an endogenous neuroprotective mechanism in the brain and limit glutamate excitotoxieity. The strategy may represent a new therapeutic approach to secondary brain damage after traumatic brain injury.

关 键 词：颅脑损伤 N-乙酰天冬氨酰谷氨酸 谷氨酸 兴奋毒性 神经保护 

分 类 号：R686[医药卫生—骨科学]