可溶性环氧化物水解酶抑制剂TPPU对大鼠局灶脑缺血后血脑屏障的保护作用

目的:研究可溶性表氧化物水解酶抑制剂(sEHi)TPPU对脑缺血/再灌注损伤所致血脑屏障(BBB)破坏的作用。方法:线栓法建立大鼠大脑中动脉缺血(MCAO)模型;45只大鼠随机分为3组,假手术组、模型组(制作MCAO模型)、TPPU组(于MCAO术前24 h、缺血再灌注后0、24及48 h经大鼠尾静脉注射TPPU),各15只。Garcia评分法评估神经功能缺损及恢复情况;TTC法检测大鼠脑梗死体积;干湿重法评估脑水肿程度;伊文氏蓝(EB)法检测BBB通透性;免疫荧光染色、western blot等方法检测BBB相关蛋白含量的变化。结果:与模型组比较,TPPU能够改善大鼠脑梗死后神经功能缺损症状(P0.01),减小脑皮质梗死体积,减少EB向脑组织渗漏,减轻血管性脑水肿,减轻MCAO后BBB紧密连接蛋白的丢失(均P0.05)。结论:TPPU能够保护MCAO大鼠BBB完整性,减轻脑水肿,减小脑梗死体积,减轻神经功能缺损症状。

The Protective Effects of Soluble Epoxidehydrolase Inhibitor TPPU on Blood Brain Barrier following Cerebral Ischemia in Rats

Objective:To investigate the effect of soluble epoxidehydrolase inhibitor (sEHi) TPPU on blood brain barrier (BBB) function in rats after focal ischemia.Methods:Rat focal cerebral ischemia model was established by transient middle cerebral artery occlusion (MCAO) via intraluminal suture.Forty-five male SD rats were randomly divided into three groups:the sham group,MCAO group and TPPU group (n=15 respectively).Neurologic deficits and behavioral function recovery were assessed by Garcia neurological severity score.The degree of cerebral edema was evaluated by dry/wet weight method.The infarct volume was evaluated by TTC staining.BBB permeability was determined by detecting the leakage of Evens Blue (EB) dye in the brain tissue.Immunofluorescent staining and western blotting were used to observe the content changes of tight junction proteins of BBB.Results:Compared with those in the MCAO group,the treatment of TPPU helped to improve the neurological deficits,decrease the infarct volume of cerebral cortex,reduce the vasogenic brain edema,decrease the leakage of EB in brain tissue and alleviate the loss of tight junction proteins in BBB (P＜0.05).Conclusion:TPPU plays an active role in protecting the BBB integrity,mitigating cerebral edema,decreasing infarct volume and ameliorating the neurological deficit in rats after MCAO.