ZL006阻断PSD-95信号途径调节线粒体功能在创伤性脑损伤中的作用  

Inhibition of PSD-95 signaling by ZL006 regulating traumatic brain injury and mitochondrial function

作　　者：蒋子剑[1,2] 杨甜[1,3] 马文科[1] 杨悦凡[1] 饶维[1] 彭程[1] 罗鹏[1] 

机构地区：[1]第四军医大学西京医院神经外科,陕西西安710032 [2]第四军医大学学员一旅,陕西西安710032 [3]西安交通大学医学部,陕西西安710061

出　　处：《中华神经外科疾病研究杂志》2015年第6期519-522,共4页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金青年项目资助项目(81301037);国家自然科学基金重点项目资助项目(81430043)

摘　　要：目的通过建立小鼠创伤性脑损伤(TBI)模型,研究ZL006调控PSD-95信号途径在TBI中的作用和机制。方法建立小鼠TBI模型,加入ZL006(1.0 mg/kg i.p.),通过脑干湿重检测和神经功能学评分评估其对TBI的作用;利用Western blot检测PSD-95和神经元型一氧化氮合酶(n NOS)的表达;并进一步采用ELISA试剂盒检测蛋白质羰基(PC)、4-羟基壬烯酸(4-HNE)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的含量。结果 ZL006可减少TBI后的脑组织含水量,改善神经功能学评分,减少PC和4-HNE的表达,增加SOD和CAT的含量,但对PSD-95和n NOS的表达水平无显著影响。结论 TBI后,ZL006可以减轻脑水肿反应并改善神经功能,但与调节PSD-95和n NOS的表达无关,而是减轻其下游线粒体损伤和氧化应激反应,进而发挥脑保护效应。Objective 3＇he study aims to investigate that ZL006 regulates PSD-95 signaling and its underlying mechanism by establishment of mouse traumatic brain injury （TBI） model. Methods After establishment of mouse TBI model and administration of ZL006 （1.0 mg/kg i. p. ） , brain water content and neurological severity score were tested to evaluate the effects of ZL006 on TBI. Expressions of PSD-95 and neuronal nitric oxide synthase （nNOS） were assayed by Western blot. Protein carbonyl （PC）, 4-hydroxynonenal （4-HNE）, superoxide dismutase （SOD）, and catalase （CAT） were examined by ELISA kits. Results Administration of ZL006 reduced the brain water content, improved the neurological severity score, decreased PC and 4-HNE, and increased SOD and CAT. However, it did not affect the expressions of PSD-95 and nNOS. Conclusion After TBI, ZL006 reduced the brain edema and improved the neurological function without the regulation of PSD-95 and nNOS expression. ZL006 plays a neuroprotective role in TBI via reducing the mitochondrial dysfunction and oxidative stress.

关 键 词：创伤性脑损伤 突触后致密物质 氧化应激反应 线粒体功能 

分 类 号：R651[医药卫生—外科学]