“活血开窍汤”对MCAO模型大鼠血脑屏障通透性的时效性影响

Effects of “Huoxue Kaiqiao” decoction on the behavior and blood-brain barrier in middle cerebral artery occlusion rats

[目的]探讨"活血开窍汤"不同给药时间对大脑中动脉梗死(MCAO)模型大鼠神经功能恢复及血脑屏障的时效性影响。[方法]将48只MCAO模型Wistar大鼠随机分为模型组及活血开窍汤治疗组(Ⅰ组:造模后2 h给药组;Ⅱ组:造模后24 h给药组;Ⅲ组:造模后48 h给药组),每组12只,另有12只大鼠作为假手术组。采用Zealonga评分法观察各组大鼠神经功能缺损情况,取材前2 h于尾静脉注射伊文思蓝(EB)溶液以观察各组大鼠血脑屏障(BBB)的通透性,免疫组化法观察各组大鼠脑组织Claudin-5蛋白含量情况。[结果]各治疗组大鼠神经功能较模型组均有改善,且差异具有统计学意义(P<0.05)。活血开窍汤Ⅱ、Ⅲ组大鼠脑缺血侧纹状体EB含量低于模型对照组(P<0.05),Claudin-5蛋白含量相对较高(P<0.05)。而活血开窍汤Ⅰ组与模型对照组相比,活血开窍汤Ⅱ组与Ⅲ组相比,差异均无统计学意义(P>0.05)。[结论]活血开窍汤可通过减轻BBB通透性,减少Claudin-5蛋白的破坏从而保护MCAO大鼠血脑屏障,但在急性期对BBB的保护作用并不十分明显,且尚不能证明在非急性期越早给予活血开窍汤对BBB的保护作用就越显著。

[Objective] To investigate the time-effect relationship of 'Huoxue Kaiqiao' decoction on the behavior and blood-brain barrier(BBB) in middle cerebral artery occlusion rats. [Methods] The 48 MCAO Wistar model rats were randomly divided into model group and'Huoxue Kaiqiao' decoction groups(group I: administration 2 hours after modeling; group II: administration 24 hours after modeling and group III: administration 48 hours after modeling). Each group contained 12 rats, and another 12 rats made up sham operation group. Zealonga scoring method was used to observe the neurological deficit situation of rats. Two hours before death from intravenous injection of EB solution in order to observe changes in BBB permeability, and another taking fixed brain to detect Claudin-5 protein content by immunohistochemistry method. [Results] Compared with the control group, nerve function were improved in all treatment groups(P<0.05).Cerebral ischemic striatum EB in treatment group Ⅱ and Ⅲ were lower than the model group(P<0.05), but the content of Claudin-5 in these groups were high(P<0.05). However, the difference was not statistically significant between group Ⅱ and group Ⅲ, and between group I and model group(P>0.05). [Conclusion] Resuscitation promoting blood circulation by reducing BBB permeability soup can reduce damage Claudin-5 protein in rat brain barrier to protect MCAO, but the protective effect in the acute phase of the BBB is not obvious, and yet could not prove that in the non-acute phase sooner promoting blood circulation giving resuscitation BBB decoction of the more remarkable.