Effect of exogenous transforming growth factor-1 on blood brain barrier permeability after status epilepticus in rats
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摘要: 目的:探讨经鼻腔给予外源性转化生长因子1(transforming growth factor-1,TGF-1)对大鼠癫痫持续状态(status epilepticus,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3h、6h、24h、2d、3d、4d、7d。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,24h达到峰值,后逐渐下降,7d接近正常;TGF组与模型组比较,脑内EB含量均低于模型组,6h至2d增加均有统计学意义(P0.05～P0.01)。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24h为最低,其中6h、24h、2d差异均有统计学意义(P0.05～P0.01),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-1能降低大鼠SE后BBB的通透性。Abstract: Objective:To investigate the effect of intranasal delivery of exogenous transforming growth factor-1(TGF-1) 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(P0.05 to P0.01) 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(P0.05 to P0.01).The expression of ZO-1 protein in TGF group was lower than controlgroup.Conclusions:Intranasal delivery of exogenous TGF-1 decreases BBB permeability after SE.
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Keywords:
- status epilepticus /
- transforming growth factor- /
- 1 /
- blood brain barrier /
- rats
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