FTY720改善颅脑损伤大鼠认知功能及其机制的研究  

Study on Improvement of FTY720 on Cognitive Function in Rats with Traumatic Brain Injury and Related Mechanism

作　　者：林群[1] 蔡建勇[1] 吴艳[1] 巴华君[1] 陆川[1] 陈献东[1] 陈茂华 孙军[1] 郑伟民[2] 

机构地区：[1]温州市中心医院,温州医科大学定理临床学院神经外科,浙江温州325200 [2]温州医科大学附属第一医院,浙江温州325000

出　　处：《中国现代应用药学》2016年第7期866-871,共6页Chinese Journal of Modern Applied Pharmacy

基　　金：浙江省科技计划项目(2014C37029)

摘　　要：目的研究FTY720对颅脑损伤大鼠认知功能的影响及相关机制。方法选用健康Wistar大鼠60只,♂,随机分成假手术组、模型组和治疗组,每组20只,采用改进的Feeney自由落体损伤装置建立大鼠颅脑损伤模型,分别于模型形成前给予-1 m L 0.9%氯化钠注射液或1 mg·kg1 FTY720腹腔注射。各组取10只大鼠,采用Morris水迷宫定位航行实验,记录大鼠逃避潜伏期,评价认知功能。另外各组取10只大鼠断头处死,分离海马组织,采用HE染色观察神经细胞形态,采用ELISA法检测脑组织白介素-1β、肿瘤坏死因子-α和白介素-6浓度。结果模型组大鼠逃避潜伏期较假手术组显著延长(P<0.05),海马组织神经细胞结构较假手术组明显破坏(P<0.05),脑组织白介素-1β、肿瘤坏死因子-α和白介素-6浓度较假手术组显著升高(P<0.05)。治疗组大鼠逃避潜伏期较模型组显著缩短(P<0.05),海马组织神经细胞结构较模型组明显恢复(P<0.05),脑组织白介素-1β、肿瘤坏死因子-α和白介素-6浓度较模型组显著下降(P<0.05)。结论 FTY720可显著改善颅脑损伤大鼠认知功能,其作用机制可能与FTY720的中枢炎症抑制作用有关。OBJECTIVE To investigate the effect of FTY720 on cognitive function in rats with traumatic brain injury and the related mechanism. METHODS All of 60 male Wistar rats were randomly divided to sham-operation group, model group and treatment group with 20 rats in each group. The rat model of traumatic brain injury was induced by a modification of-Feeney＇s weight-drop mode1. The Rats were administrated intraperitoneally with 1 m L normal saline or 1 mg·kg^-1 FTY720 respectively before procedures or trauma. A total of 10 rats in each group underwent assessment of cognitive function using localization navigation experiment from Morris water maze and with recorded escape latency. Another 10 rats in each group were killed by decapitation and then their hippocampus tissues were dissected. HE staining was performed to observe morphology of neuronal cells and ELISA was done to determine the concentrations of interleukin-1β, tumor necrosis factor-α and interleukin-6 in brain tissues. RESULTS As compared with sham-operation group, the escape latencies were markedly prolonged（P〈0.05）, the morphology of neuronal cells in the hippocampus tissues were markedly damaged（P〈0.05）, as well as the concentrations of interleukin-1β, tumor necrosis factor-α and interleukin-6 in brain tissues were obviously elevated（P〈0.05） in model group. Compared with model group, the escape latencies were markedly shortened（P〈0.05）, the morphology of neuronal cells in the hippocampus tissues were markedly recovered（P〈0.05）, as well as the concentrations of interleukin-1β, tumor necrosis factor-α and interleukin-6 in brain tissues were obviously decreased（P〈0.05） in treatment group. CONCLUSION FTY720 can markedly improve the cognitive function of rats with traumatic brain injury and its mechanism may be related to the inhibition of FTY720 on inflammation in central nervous system.

关 键 词：FTY720 认知功能 炎症反应 脑保护作用 

分 类 号：R965.2[医药卫生—药理学]