外源性转化生长因子β1对大鼠癫痫持续状态后血脑屏障通透性的影响

Effect of exogenous transforming growth factor-β1 on blood brain barrier permeability after status epilepticus in rats

目的:探讨经鼻腔给予外源性转化生长因子β1(transforming growth factor-β1,TGF-β1)对大鼠癫痫持续状态(statusepilepticus,SE)后血脑屏障(blood brain barrier,BBB)通透性的影响。方法:建立匹罗卡品(pilocarpine)SE模型。SD大鼠252只随机分成正常对照组、模型组和TGF组,各组设计7个观察时间点,即SE后3 h、6 h、24 h、2 d、3 d、4 d、7 d。各大鼠在相应的时间点处死取材,应用化学定量的方法检测大鼠脑组织内伊文思蓝(Evans blue,EB)的含量,应用免疫组织化学法检测相应时间点海马区的zonula occluden-1(ZO-1)蛋白的表达。结果:大鼠脑内的EB含量与正常对照组相比,模型组和TGF组都先增加,24 h达到峰值,后逐渐下降,7 d接近正常;TGF组与模型组比较,脑内EB含量均低于模型组,6 h至2 d增加均有统计学意义(P<0.05～P<0.01)。TGF组和模型组比较,海马区ZO-1蛋白的表达都是先降后升,以24 h为最低,其中6 h、24 h、2 d差异均有统计学意义(P<0.05～P<0.01),TGF组明显高于模型组,低于正常对照组。结论:经鼻腔给予外源性TGF-β1能降低大鼠SE后BBB的通透性。

Objective： To investigate the effect of intranasal delivery of exogenous transforming growth factor-β1 （TGF-β1） on the permeability of blood brain barrier（BBB） after status epilepticus （SE） in Sprague-Dawley rats. Methods： SE model was induced by pilocarpine. Two hundred fifty-two SD rats were divided into normal control group, model group and TGF group randomly, each of which was reassigned into seven sub-groups：3 h, 6 h, 24 h, 2 d, 3 d, 4 d and 7 d groups after SE. The change or BBB permeability was determined by detecting Evans blue （EB） content in rat brains with chemic-quantitative analysis;The protein expression of zonula occluden-1 （ZO-1） in hippocampus was analyzed by immunochemistry. Results：The EB contents in model group and TGF group were significantly increased, compared with control group, in which the peak of EB was emerged at 24 h after SE, and then decreased gradually,closed to normal at 7 d;Compared with model group,EB contents in TGF group were decreased at 6 h to 2 d（P 〈0.05 to P 〈 0.01 ） with significant difference. In model and TGF groups, the protein expression of ZO-1 was firstly declined, and then gradually increased ;the lowest expressions were emerged at 24 h after SE;and there was significant differences of ZO-1 expression at 6 h ,24 h was 2 d points between the two groups（P 〈 0.05 to P 〈 0. 0.01）. The expression of ZO-1 protein in TGF group was lower than control group. Conclusions：Intranasal delivery of exogenous TGF-β1 decreases BBB permeability after SE.