中华神经外科杂志
中華神經外科雜誌
중화신경외과잡지
Chinese Journal of Neurosurgery
2009年
10期
937-940
,共4页
钟春龙%江基尧%罗其中%赵学仁%Bruce G.Lyeth
鐘春龍%江基堯%囉其中%趙學仁%Bruce G.Lyeth
종춘룡%강기요%라기중%조학인%Bruce G.Lyeth
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
顱腦損傷%N-乙酰天鼕氨酰穀氨痠%穀氨痠%興奮毒性%神經保護
로뇌손상%N-을선천동안선곡안산%곡안산%흥강독성%신경보호
Traumatic brain injury%N-acetylaspartylglutamatc (NAAG)%Glutamate%Excitotoxicity%Neuroprotection
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,8 h,16 h)分别经腹腔注射新型NAAG肽酶抑制剂ZJ-43(各组剂量:0,50,100,150 mg/kg).伤后24 h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(50 mg/kg)保护作用最佳,还能同时显著减少儋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.
目的 探索顱腦損傷後N-乙酰天鼕氨酰穀氨痠(NAAG)肽酶抑製的神經保護效應.方法 將20隻SD大鼠隨機分成4組後製作中度液壓顱腦損傷模型.傷後3箇時間點(即時,8 h,16 h)分彆經腹腔註射新型NAAG肽酶抑製劑ZJ-43(各組劑量:0,50,100,150 mg/kg).傷後24 h處死動物取腦組織行Fluoro-Jade B組織熒光染色以及GFAP免疫組化染色.通過立體細胞計數著重觀察大鼠海馬CA2/3區退變神經元及正常膠質細胞的數量變化.結果 ZJ-43能顯著減少顱腦損傷後的神經元退變(P＜0.01),其中小劑量處理組(50 mg/kg)保護作用最佳,還能同時顯著減少儋顱腦損傷後的膠質細胞丟失(P＜0.05).結論 阻斷NAAG肽酶活性能有效放大內源性遞質NAAG的神經保護作用,從而阻斷穀氨痠興奮毒性的病理進程,有望成為治療顱腦損傷的新策略.
목적 탐색로뇌손상후N-을선천동안선곡안산(NAAG)태매억제적신경보호효응.방법 장20지SD대서수궤분성4조후제작중도액압로뇌손상모형.상후3개시간점(즉시,8 h,16 h)분별경복강주사신형NAAG태매억제제ZJ-43(각조제량:0,50,100,150 mg/kg).상후24 h처사동물취뇌조직행Fluoro-Jade B조직형광염색이급GFAP면역조화염색.통과입체세포계수착중관찰대서해마CA2/3구퇴변신경원급정상효질세포적수량변화.결과 ZJ-43능현저감소로뇌손상후적신경원퇴변(P＜0.01),기중소제량처리조(50 mg/kg)보호작용최가,환능동시현저감소담로뇌손상후적효질세포주실(P＜0.05).결론 조단NAAG태매활성능유효방대내원성체질NAAG적신경보호작용,종이조단곡안산흥강독성적병리진정,유망성위치료로뇌손상적신책략.
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 in4 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 Histofluorescence and GFAP Immunohistochemistry protocols,lpsilateral 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 excitotoxicity.The strategy may represent a new therapeutic approach to secondary brain damage after traumatic brain injury.
