通腑法开通玄府对MCAO大鼠脑AQP4mRNA表达的影响

目的研究通腑醒神胶囊（简称TFXSJN）通腑法开通玄府对大鼠大脑中动脉阻塞（Middle cerebral artery occlusion,简称MCAO）模型脑组织水通道蛋白4（Aqμaporin-4,简称AQP-4）mRNA表达的影响。方法采用线栓法制作大鼠MCAO模型,2h后拔线造成缺血再灌注损伤。观察拔线后12h、1d、2d、3d及7d不同时间点大鼠神经行为评分、脑组织AQP-4mRNA的表达水平,以及各组大鼠在1d、3d及7d时脑含水量变化。结果TFXSJN治疗后能明显减轻大鼠在1d、2d、3d及7d时的神经功能评分,与模型组比较P〈0.05或P〈0.01;造模后,TFXSJN组及模型组大鼠脑含水量在1d及3d时均明显高于假手术组及正常组,具有显著差异（P〈0.01）,以3d时的脑含水量最高,7d时4组大鼠的脑含水量无显著差异（P〉0.05）;与模型组比较,TFXSJN组3d时脑含水量明显降低（P〈0.01）;TFXSJN组及模型组大鼠脑组织损伤侧AQP-4mRNA的表达在12h时已经明显升高,与健侧、假手术及正常组比较均有显著差异（P〈0.05）;模型组在3d时达高峰,TFXSJN组在2d时达高峰,3d时已有所下降,与模型组损伤侧比较有显著差异（P〈0.05）,但仍高于健侧（P〈0.05）。7d时两组损伤侧的AQP-4mRNA表达水平基本恢复正常,与健侧、假手术及正常组比较无显著差异（P〉0.05）。假手术组在各时点内其损伤侧AQP-4mRNA表达水平与健侧及正常组比较均无显著差异（P〉0.05）。结论急性脑缺血再灌注损伤时存在AQP-4mRNA基因表达的上调。12h时即明显升高,3d时达高峰,7d时基本恢复正常。AQP-4mRNA表达的上调可能与缺血性脑水肿的形成密切相关,而TFXSJN通腑法开通玄府法能够调节缺血再灌注损伤后AQP-4mRNA表达的失衡状态,减轻缺血后脑水肿,其调节AQP-4mRNA基因的异常表达可能是通腑法开通玄府治疗缺血性中风的分子机制之一。因此推测玄府与神经细胞膜上通道蛋白（如AQP-4等）之间可能存在共同的实质内涵。

Effects of "Tongfu Xingshen Capsule" on Cerebral Aquaporin-4 Expression in Middle Cerebral Artery Occlusion Rats

Objective To study the effects of "Tongfu Xingshen Capsule"on the cerebral Aquaporin-4 expression in middle cerebral artery occlusion(MCAO) rats.Method Ligation was adopted to make acute focal cerebral ischemia and removed 2 hours later to cause reperfusion injury.The neurobehavioral score and AQP-4 mRNA expression were observed at 12 hours,1 day,2 days,3 days and 7 days afteroperation and treatment.The brain water content was measured at 1 day,3 days and 7 days after operation.Results After treatment by "Tongfu Xingshen Capsule",the rats' neurobehavioral score was reduced at 1 day,2 days,3 days and 7 days,with significant differences in comparison with model group's(P < 0.05 or P < 0.01);after operation,the brain water contents in treatment group and model group at 1 day and 3 days were significantly higher than those in sham group's and normal group's(P < 0.01).At 3 days,the brain water content was maximum;at 7 days,all four groups had no significant difference(P > 0.05);compared with model group's,the brain water content at 3 days of treatment group's was decreased with significant differences(P < 0.01);compared with the contralateral side,the expression of AQP-4 mRNA of affected side of treatment and model groups'were increased significantly at 12 hours(P < 0.01),the model's peaking at 3 days,while the Capsule's peaking at 2 days and reduced at 3 days,compared with the model' s there was a significant difference(P < 0.05);at 7 days,both returned to normal;compared with the contralateral side,the sham group and the normal control group showed no significant difference(P > 0.05).Conclusion In acute cerebral ischemia-reperfusion injury,AQP-4mRNA gene expression up-regulates.It significantly increases at 12 hours,peaking at 3 days,and returning to normal at 7 days.The up-regulation of AQP-4mRNA expression may be closely related to the ischemic brain edema formation.This Capsule can adjust the expression of AQP-4mRNA of ischemia-reperfusion injury,reduce ischemic brain edema,which plays a role of neuroprotective effect.Regulating the abnormal expression of AQP-4mRNA gene may be one of the molecular mechanisms of"Tongfu Xingshen Capsule"in the treatment of ischemic stroke.Therefore,we presume that there may be some common substances between sweat pores and nerve membrane channel proteins such as AQP-4.