芬戈莫德对创伤性脑损伤小鼠学习和记忆能力的影响

摘要

Objective To investigate the effect of fingolimod(FTY-720)on learning and mem⁃ory capacity after traumatic brain injury(TBI). Methods Forty-eight C57BL/6 mice were randomly di⁃vided into sham group, TBI group and FTY-720 treated group(TBI+FTY group). TBI model was in⁃duced by control cortical injury device; rats in TBI+FTY group were administrated with FTY-720 intra⁃peritoneally following TBI. Expression of cleaved caspase-3 and B cell lymphoma(Bcl-2)in hippocam⁃pus was determined by Western-blotting. The learning and memory capacity was evaluated by Morris wa⁃ter maze(MWM)test. Results Compared to sham group, the expression of cleaved caspase-3 was in⁃creased and the Bcl-2 level was reduced in TBI group. In addition, the escape latency was prolonged and the times of platform crossing and duration in target quadrant were decreased after TBI. Administration of FTY-720 could not only reverse the cleaved caspase-3 and Bcl-2 expression, but also prevent the al⁃terations of escape latency, platform crossing times and duration in target quadrant induced by TBI. Con-clusion TBI-triggered hippocampal cellular apoptosis and cognitive dysfunction could be effectively rescued by FTY-720.%目的：探讨芬戈莫德（FTY-720）对创伤性脑损伤（TBI）小鼠学习和记忆能力的影响作用。方法将48只C57BL/6小鼠随机均分为假损伤组、TBI模型组、FTY-720治疗组（TBI+FTY组）。采用控制性皮层损伤法制备小鼠TBI模型，治疗组予以腹腔注射FTY-720。Western-blotting检测海马区活化型半胱天冬酶-3（cleaved caspase-3）和 B 细胞淋巴瘤-2（Bcl-2）的表达水平。Morris 水迷宫试验评估小鼠学习与记忆能力。结果与假损伤组比较，TBI 组海马区cleaved cas⁃pase-3的表达增加，Bcl-2的表达下降，小鼠的逃避潜伏期时间延长，平台象限的停留时间和穿越次数减少（P＜0.05）。与TBI组比较，TBI+FTY组的cleaved caspase-3的表达减少，Bcl-2的表达显著增加，小鼠的逃避潜伏期时间缩短，平台象限的停留时间和穿越次数显著增加（P＜0.05）。结论 TBI可引起海马区细胞凋亡增加和学习记忆能力减退，FTY-720可有效地减少细胞凋亡程度和改善TBI后认知功能障碍。