高迁移率族蛋白1抑制剂甘草酸对大鼠癫痫持续状态后血脑屏障的影响

目的研究高迁移率族蛋白1(HMGB 1)在大鼠癫痫持续状态后的表达情况,以及给予HMGB 1抑制剂甘草酸干预对大鼠癫痫持续状态后血脑屏障的影响。方法将SD大鼠随机分为3 h对照组、癫痫3 h组、癫痫24 h组和癫痫72 h组,每组8只。癫痫组构建癫痫持续状态模型后,分别于癫痫造模成功后3 h、24 h、72 h处死,3 h对照组则在对应时间点给予等量生理盐水,并在匹罗卡品注射时间点后3 h处死,所有大鼠处死后提取海马组织,利用Westren-blot法检测HMGB 1蛋白表达情况。将大鼠随机分为对照组、癫痫组、甘草酸干预组(GA 30 mg/kg),每组8只,癫痫组及甘草酸干预组均采用上述方法造模,此外,甘草酸干预组在癫痫造模成功后2 h给予30 mg/kg甘草酸腹腔注射,其余两组则在对应时间点给予等量生理盐水,3组大鼠均在癫痫造模成功后24 h处死,取大脑测定伊文思蓝渗出量。结果 HMGB 1表达情况:癫痫3 h组较3 h对照组表达增加(P0.05);癫痫24 h组较癫痫3 h组表达进一步增高(P0.05);癫痫72 h组较癫痫24 h组表达有所下降(P0.05)。伊文思蓝渗出情况:癫痫持续状态后24 h,癫痫组较对照组渗出量增加(P0.05);甘草酸干预组较癫痫组渗出量明显减少(P0.05)。结论大鼠癫痫持续状态后可出现HMGB 1表达增高以及血脑屏障受损,在给予HMGB 1活性抑制剂甘草酸干预后可减轻癫痫对大鼠血脑屏障完整性的破坏。

Effects of high-mobility group box 1 inhibitor glycyrrhizic acid on blood-brain barrier of rats after status epilepticus

Objective To investigate the expression of high-mobility group box 1(HMGB1) in rats after status epilepticus and the effects of HMGB1 inhibitor glycyrrhizic acid on the blood-brain barrier of rats after status epilepticus.Methods Sprague-Dawley rats were randomly divided into 3-h control group, 3-h epilepticus group, 24-h epilepticus group, and 72-h epilepticus group, with 8 rats in each group. After the status epilepticus model was established in epilepticus groups, rats were sacrificed at 3, 24, and 72 hours, respectively, after successful establishment of the status epilepticus model, while the rats in the 3-h control group were given injection of normal saline at corresponding time points and were sacrificed 3 hours after pilocarpine injection. Then the hippocampus tissues from all rats were collected, and Western blot was applied to measure the expression of HMGB1. Rats were randomly divided into control group, epilepticus group, and glycyrrhizic acid treatment group (GA 30 mg/kg), with 8 rats in each group, and the measures above were applied to establish the model in epilepticus group and glycyrrhizic acid treatment group. In addition, the rats in glycyrrhizic acid treatment group were given intraperitoneal injection of glycyrrhizic acid 30 mg/kg 2 hours after successful establishment of epilepticus model, and the rats in the other two groups were given injection of normal saline at corresponding time points. The rats in 3 groups were all sacrificed 24 hours after successful establishment of epilepticus model, and brain tissues were collected to measure Evans blue seepage.Results The expression of HMGB1 in the 3-h epilepticus group increased significantly compared with that in the 3-h control group (P<0.05); the expression of HMGB1 in the 24-h epilepticus group increased further compared with that in the 3-h epilepticus group (P<0.05), while the expression of HMGB1 in the 72-h epilepticus group decreased significantly compared with that in the 24-h epilepticus group (P<0.05). As for Evans blue seepage, at 24 hours after status epilepticus, Evans blue seepage in epilepticus groups increased significantly compared with that in the control group (P<0.05), and Evans blue seepage in the glycyrrhizic acid treatment group decreased significantly compared with that in the epilepticus groups (P<0.05).Conclusions Increase in expression of HMGB 1 and blood-brain barrier damage can be observed in rats after status epilepticus, and administration of HMGB 1 inhibitor glycyrrhizic acid can reduce blood-brain barrier damage.