脑疏宁对脑外伤大鼠脑水肿及脑组织AQP4表达的影响

目的 观察脑疏宁对脑外伤大鼠脑组织含水量及水通道蛋白4(AQP4)表达的影响,探讨其治疗创伤性脑水肿的机制.方法 SD大鼠264只,随机分为假手术组(88只)、模型组(88只)和脑疏宁组(88只),建立大鼠创伤性脑损伤模型.分别在6 h,1、3、5 d 4个时间点测定脑组织含水量、伊文思蓝(EB)含量,并采用免疫组化方法检测脑组织AQP4蛋白的表达,电镜观察血脑屏障超微结构改变.结果 模型组大鼠伤后各时间点伤侧脑组织含水量、EB含量及伤灶周围AQP4蛋白表达水平明显高于假手术组(均P<0.001);电镜下内皮细胞紧密连接开放、星形胶质细胞足突肿胀.中药治疗组各时间点脑组织含水量、EB含量及AQP4表达水平均较模型组降低(P<0.05);血脑屏障紧密连接的破坏减少、星形胶质细胞足突肿胀减轻.结论 脑疏宁可改善血脑屏障损伤,减轻创伤后脑水肿.其作用可能与抑制AQP4在损伤脑组织中的表达、减轻星形胶质细胞损害有关.

Effects of Naoshuning on brain water content and the protein expression of AQP4 in rats with traumatic brain injury

Objective To investigate the effects of Naoshuning,a TCM formula for activating blood circulation and alleviating water retention,on the protein expression of aquaporin4(AQP4) in experimental injured brain tissue of rats and its mechanism.Methods The SD rats were randomly divided into the sham operation group(n=88),the traumatic brain injury(TBI) group(n=88) and the Naoshuning group(n=88).Changes of brain water content,permeability of blood-brain barrier(BBB) were determined at 6 h,1 d,3 d and 5 d after TBI.Immunohistochemical technique was used to investigate the protein expression of AQP4.Results The brain water content,permeability of BBB and AQP4 protein expression of TBI group were obviously higher than those of the sham operation group(P<0.001).The electron microscope result indicated that BBB was evidently damaged 1day after TBI,with vascular endothelial cell tight junction damaged,basement membrane broken and astrocyte end feet process swelled obviously.In Naoshuning treatment group brain tissue water content,EB content and the expression of AQP4 were obviously lower than those of the model group at each time point(P<0.05).The ultramicrostructure changes could be relieved by Naoshuning.Conclusion The principle of activating blood circulation and alleviating water retention showed effects in reducing cerebral edema and protecting BBB,which may be related with inhibiting the epression of AQP4 protein.