大鼠脑挫裂伤模型的建立及损伤机制的代谢组学分析  

Establishment of rat model of cerebral contusion and laceration and the metabonomic analysis of the damage mechanism.

作　　者：刘建仁[1] 黎启明 陈燕芬[2] 易铭佳[1] 黄良文[1] 

机构地区：[1]广州中医药大学第一附属医院颅脑科,广州510405 [2]广东药学院中药学院中药方剂与药理系,广州510006

出　　处：《广东医学》2014年第14期2148-2153,共6页Guangdong Medical Journal

基　　金：广东省社会发展领域科技计划项目(编号:粤科社字[2011]106号-24)

摘　　要：目的采用自由落体打击法造模,对大鼠脑损伤后病理改变进行代谢组学分析,建立可靠的大鼠脑挫裂伤模型,为进一步的研究提供可靠的动物实验平台。方法选用SD实验大鼠,分为假手术组、20 g打击组、30 g打击组、50 g打击组。假手术组不造模,20 g打击组、30 g打击组、50 g打击组分别用20、30、50 g的砝码,采用自由落体打击法建立脑挫裂伤模型。记录打击后大鼠死残情况、神经功能缺损评分,观察脑组织病理切片,检测大鼠血浆氢谱核磁共振波谱,并作统计学分析。结果 50 g打击组大鼠死亡率最高,病理切片观察见神经细胞广泛坏死,细胞结构破坏;代谢组学分析发现血浆中抑制性氨基酸γ-羟基丁酸成倍增加,胆碱含量增加。30 g打击组神经功能缺损评分〈7分,神经细胞大量坏死,N-乙酰天门冬氨酸明显下降,乳酸含量显著升高,动物死亡率和致残率较高。20 g打击组大鼠神经功能缺损起初评分在7-8分之间,脑组织局部见少量血肿灶,神经细胞水肿较明显,N-乙酰天门冬氨酸、肌酸、γ-氨基丁酸等含量下降,谷氨酸、乳酸、胆碱含量升高;但神经功能缺损评分在术后第6、7天恢复至13-14分。结论自由落体打击后致神经元功能受损,抑制性氨基酸增多,神经抑制明显,继发细胞坏死。打击重量越大,原发脑损伤越严重,继发性损伤也越严重。20 g打击可令动物出现部分神经功能受损,兴奋性氨基酸含量升高,抑制性氨基酸含量下降引起继发脑损伤,脑组织缺血缺氧损伤较明显,但神经功能缺损在术后恢复较快,死亡率低。因此,该方法建立的动物模型病理变化显著,修复也快,过程显著并且完整,死亡率低,适合于进一步研究需要,是理想的脑挫裂伤动物模型。Objective Ion for animal experiment using free falling impact,toion for animal experiment using free falling impact,to further research the metabonomics changes in injury. Methods SD rats were divided into sham operation group,20 g group,30 g group and 50 g group. The rats in sham operation group were not modeled. The rats in 20 g group,30 g group and 50 g group were impacted by the free falling objects weighing 20 g,30 g and 50 g,respectively,to establish the models of cerebral contusion and laceration. The rat mortality and neurological function deficit score were recorded. The cerebral pathological slice was observed. The rat plasma was scanned with hydrogen nuclear magnetic resonance spectroscopy pop technique. Results Extensive deaths were observed in 50 g group,with major neuron necrosis and destruction in pathological observation,also increase of choline content and reduction of γ- hydroxyl butyrate in plasma. Neurological deficit score was lower than 7 in 30 g group,with neuron necrosis observed. Significant reduction in N-acetyl aspartic acid and increase in lactic acid were also observed in 30 g group,so were the high mortality and disability.The neurological deficit score was between 7 and 8 in 20 g group,with mild cerebral hematoma and significant neuron edema. Reductions in N- acetyl aspartic acid,creatine and γ- aminobutyric acid were observed,while increases of glutamate,lactic acid and alkali were also observed in 20 g group. However,the neurological deficit score was recovered between 13 and 14 on the 6^thand 7^thday. Conclusion Neurological function impairment could by induced by free falling object impact,resulting increase of inhibitory amino acids,neural inhibition and secondary necrosis. The greater weight produces server primary brain injury as well was severer secondary injury. The free falling object impact by 20 g produces partial neurological function impairment,up- regulation of excitatory amino acids and down- regulation of inhibitory amino acids,thus further induces secondary brain

关 键 词：脑挫裂伤模型 代谢组学 病理切片 核磁共振波谱技术 

分 类 号：R651.15[医药卫生—外科学]