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

关键词:  FTY720  认知功能  炎症反应  脑保护作用

Key words:  FTY720  cognitive function  inflammation  cerebral protective effect

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 mL 0.9%氯化钠注射液或1 mg·kg^-1 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。

Abstract:

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 mL 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-1b, tumor necrosis factor-a 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-1b, tumor necrosis factor-a 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-1b, tumor necrosis factor-a 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.