目的 探討銀杏內(nèi)酯B（GB）對癲癇模型大鼠血腦屏障（BBB）通透性的保護(hù)作用及機(jī)制。方法 將180只雄性SD大鼠按隨機(jī)數(shù)字表法分為對照組（生理鹽水）、模型組（生理鹽水）、丙戊酸鈉（VPA，300 mg/kg）組和GB低、中、高劑量（2.5、5.0、10.0 mg/kg）組，每組30只。采用氯化鋰-匹羅卡品誘導(dǎo)制備癲癇大鼠模型；sc匹羅卡品前1 h，各組分別ip給藥。觀察各組大鼠癲癇發(fā)作潛伏期及持續(xù)時間；干濕比質(zhì)量法測定腦組織含水量，伊文思藍(lán)滲透法測定BBB通透性；黃嘌呤氧化法和鉬酸銨法分別檢測腦組織超氧化物歧化酶（SOD）、過氧化氫酶（CAT）活力，硫代巴比妥酸法檢測丙二醛（MDA）含量，酶聯(lián)免疫吸附法檢測腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素-1β（IL-1β）、白細(xì)胞介素-6（IL-6）含量，Western blotting檢測閉合蛋白（Occludin）、閉鎖連接蛋白-1（ZO-1）、腦組織基質(zhì)金屬蛋白酶-2（MMP-2）、腦組織基質(zhì)金屬蛋白酶-9（MMP-9）蛋白表達(dá)。結(jié)果 與模型組比較，VPA組和GB中、高劑量組大鼠癲癇發(fā)作潛伏期顯著延長、發(fā)作持續(xù)時間縮短（P<0.01）；腦組織含水量和伊文思藍(lán)滲透量顯著降低（P<0.05、0.01）；腦組織SOD和CAT活性顯著升高且MDA、TNF-α、IL-1β、IL-6含量顯著降低（P<0.05、0.01）；Occludin、ZO-1表達(dá)顯著上調(diào)且MMP-2、MMP-9表達(dá)顯著下調(diào)（P<0.01）；且GB高劑量組作用優(yōu)于VPA組。結(jié)論 GB對癲癇大鼠BBB通透性具有保護(hù)作用，其機(jī)制可能與抑制氧化應(yīng)激和炎癥，以及上調(diào)Occludin、ZO-1表達(dá)并下調(diào)MMP-2、MMP-9表達(dá)有關(guān)。

Objective To investigate the protective effect of ginkgolide B (GB) on the permeability of blood-brain barrier (BBB) in rats with epilepticus (EP) and its mechanism. Methods Totally 180 male SD rats were randomly divided into normal control group (normal saline), model group (normal saline), sodium valproate (VPA) group (300 mg/kg) and GB low, medium and high dose groups (2.5, 5.0, 10.0 mg/kg). The EP rat models were pruducted by induction with lithium chloride and pilocarpine; 1h before pilocarpine injection, the drugs were given to rats in each group by administered intraperitoneally. The behavior of rats in each group was observed; the water content of brain tissue was detected by wet and dry specific gravity method, and the permeability of BBB was detected by Evans blue penetration method. The activity of SOD and CAT were detected by xanthine oxidation method and ammonium molybdate method, and the MDA content was detected by thiobarbituric acid method; the content of TNF-α, IL-1β, IL-6 were detected by ELISA. The expression of Occludin, ZO-1, MMP-2, MMP-9 were detected by Western blotting method. Results Compared with model group, the number of seizures of the rats in VPA group and GB medium, high dose groups was reduced, the seizure duration was shortened (P<0.01). The brain tissue water content and Evans blue penetration were reduced (P<0.05 or 0.01). The activity of SOD, CAT in brain tissue were increased and MDA, TNF-α, IL-1β, IL-6 content were decreased (P<0.05 or 0.01); the expression of Occludin, ZO-1 were up-regulated and MMP-2, MMP-9 expression were down-regulated (P<0.01). Compared with VPA group, the number of seizures of the rats in GB high dose group was reduced, and the seizure duration was shortened (P<0.05 or 0.01). The Evans blue penetration were reduced (P<0.05). The activity of SOD in brain tissue were increased and MDA, TNF-α, IL-6 content were decreased (P<0.05 or 0.01); the expression of Occludin, ZO-1 were up-regulated and MMP-2, MMP-9 were down-regulated (P<0.05 or 0.01). Conclusion GB has protective effect on the BBB permeability of EP rats; which may be related to the inhibition of oxidative stress and inflammation, as well as the up-regulation of Occludin, ZO-1 expression and down-regulation of MMP-2, MMP-9 expression.

R285.5

河北省醫(yī)學(xué)科學(xué)研究課題計(jì)劃（20191789）