闭锁小带蛋白-1在脑外伤后皮质中的表达变化

Expression of Zonula Occludens-1 in Cerebral Cortex Following Traumatic Brain Injury

目的：观察闭锁小带蛋白-1（zonula occludens-1，ZO-1）在脑外伤后皮质中不同时段的表达变化。方法建立小鼠脑外伤模型，分为脑外伤后1h、3h、6h、12h、24h、3d、7d组，同时设立假手术组及正常对照组。脑皮质中伊文思蓝（Evans blue，EB）含量检测评估血脑屏障通透性，Western印迹法和免疫组织化学染色法检测损伤皮质区ZO-1的表达。结果脑外伤后1 h皮质中EB含量开始增加，伤后1-3 d达高峰，伤后7 d接近正常。 Western印迹法显示，ZO-1在损伤1 h后表达下调，损伤1-3 d达到最低值，损伤7 d后明显回升，但仍低于假手术组和正常对照组。免疫组织化学染色显示，正常脑皮质血管中ZO-1呈强阳性表达，损伤后表达逐渐减弱，损伤3 d后阳性表达几乎消失，之后逐渐恢复。结论 ZO-1在脑外伤后皮质区呈先降低后升高的表达规律，与脑外伤后血脑屏障通透性变化规律呈负相关，为推断脑外伤损伤时间提供了新指标。

Objective To observe the time-course expression of zonula occludens-1 （ZO-1） in cerebral cortex after traumatic brain injury （TBI）. Methods The TBI model of mouse was established. The mice were divided in 1 h, 3 h, 6 h, 12 h, 24 h, 3 d, 7 d after TBI, shamand control groups. The permeability of the blood brain barrier was evaluated by measuring the extravasation of Evans blue （EB） dye. The expression of Z O-1 in cerebral cortex in the injured area was detected by western blotting and im-munohistochemistry. Results The extravasation of EBdye of injured cortex gradually increased from 1 h, peaked at 1-3 d and approximately decreased to normal at 7 d after TBI. western blotting revealed that the expression of Z O-1 gradually decreased after 1 h, was at the lowest at 1-3 d, and then significantly increased after 7 d but was still lower than that of normal and shamgroups. The result of immunohisto-chemistry showed that Z O-1 had strong expression in vessel of normal cortex, gradually decreased after TBI, and almost disappeared at 3 d after TBI and gradually recovered to normal level later. Conclusion The expression of Z O-1 in the injured cortex after TBI initially decreases and then increases. The nega-tive correlation between Z O-1 expression and EBextravasation after TBI could be used as a newindi-cator for wound age estimation.