低压低氧后处理对创伤性脑损伤大鼠神经功能预后的影响

Effect of hypobaric hypoxia postconditioning on neurological function prognosis in traumatic brain injury rats

目的探讨低压低氧后处理(HHP)对创伤性脑损伤(TBI)大鼠神经功能预后的影响。方法 48只Wistar大鼠随机分为假手术组(sham组,n=12)、单纯颅脑创伤组(fpi组,n=18)和HHP组(n=18)。fpi组和HHP组采用液压冲击损伤(FPI)的方法建立TBI模型,HHP组于建模后3 h进行为期3 d,每天2 h的HHP干预。通过Morris水迷宫(MWM)、转棒和旷场实验检测大鼠学习记忆、运动协调能力和焦虑抑郁样行为;利用尼氏染色法检测海马神经元的存活情况。结果 MWM实验中fpi组大鼠学习记忆能力低于sham组和HHP组(F=4.257 6,P<0.05),HHP组和sham组差异无统计学意义(P>0.05);转棒实验中,HHP组大鼠运动协调能力低于sham组(F=4.335,P<0.05),fpi组和sham组差异无统计学意义(P>0.05);旷场实验中fpi组大鼠表现出典型的焦虑抑郁样行为,HHP组和sham组大鼠表现差异无统计学意义(P>0.05);海马尼氏染色结果显示3组大鼠造模后3 d伤侧海马CA1和CA3区存活神经元数量差异无统计学意义(P>0.05);fpi组造模后24 d伤侧海马CA1和CA3区存活神经元数量较sham组和HHP组减少(F=46.758、5.486,P<0.05)。结论 TBI可造成大鼠学习记忆损害和焦虑抑郁,并导致海马神经元死亡。首次发现HHP对TBI大鼠的神经功能预后具有双重作用,虽能消除TBI后的学习记忆损害和焦虑抑郁样行为,降低海马神经元死亡,但同时也会损害大鼠的运动协调能力。

Objective To investigate the effect of hypobaric hypoxia postconditioning（ HHP） on neurological function prognosis in traumatic brain injury（ TBI） rats. Methods 48 adult male Wistar rats were randomly divided into sham group（n=12）,fpi group（n=18） and HHP group（n=18）. The rat model of TBI was made by the method of fluid percussion injury（ FPI） and rats in HHP group were submitted to HHP（360 Torr,2 h,3 trails spaced at 24 h） starting 3 h after FPI. The learning and memory abilitiy,motor coordination,anxiety and depression-like behaviors and surviving neurons of ipsilateral hippocampus were evaluated by Morris water maze（ MWM） ,rotatord test,open-field test and hippocampus nissl stain respectly. Results Morris water maze：compared with sham and HHP group, learning and memory abilitiy of rats in fpi group were significantly decreased（F=4. 257 6,P〈0. 05）,whereas no difference was observed between sham and HHP group（P〉0. 05）;Rotatord test：compared with sham group,motor coordination of rats in HHP group were significantly decreased （ F=4. 335 , P〈0. 05 ） , whereas no difference was observed between sham and fpi group （ P 〉0. 05 ）;Open-field test：compared with sham group, rats of fpi group showed significant anxiety and depression-like behavioral changes, whereas no difference was observed between sham and HHP group;Nissl stain：No difference of surviving neurons of ipsilateral hippocampus CA1 and CA3 region was observed among three gourps at 3 d after FPI（P〉0. 05）. There were significantly fewer surviving neurons of ipsilateral hippocampus CA1 and CA3 region in fpi group than sham and HHP group at 24 d after FPI （ F =46. 758,5. 486,P〈0. 05）. Conclusion TBI induces learning and memory impairment,anxiety and depression-like behaviors and neurons death in hippocampus. HHP was first discovered having double effects on neurological function prognosis in TBI rats. On the one hand,HHP can remove the impairment of learning and memory,anxiety and depression-like behaviors and neurons death in hippocampus;on the other hand,HHP impairs motor coordination at the same time.