摘要
目的:探讨高迁移率族蛋白B1(high mobility group box 1,HMGB1)拮抗剂BoxA对癫痫大鼠发作与海马损伤的影响。方法:将雄性SD大鼠随机分为假手术组、癫痫模型(EP)组和高、中、低剂量BoxA干预组;海马微量注射海人酸制作癫痫大鼠模型,造模前侧脑室注射不同剂量BoxA对大鼠进行干预,其中假手术组海马及侧脑室分别注射等体积生理盐水。记录各组大鼠达到Ⅲ级发作的潜伏时间(seizure onset time,SOT),作为评价癫痫发作易感性指标;HE染色观察脑组织病理变化,NeuN免疫组化染色评价海马神经元丢失情况,作为评价脑组织损伤指标,磷酸化细胞核因子κB-p65(p-NFκB-p65)免疫组化染色观察其表达情况。结果:高、中、低剂量BoxA干预组大鼠SOT均显著长于EP组(P<0.05);与EP组相比,BoxA干预组海马组织损伤均明显减轻,神经元丢失减少(P<0.05);高剂量BoxA干预组较中低剂量干预组SOT延长、脑组织损伤程度减轻,但差异无统计学意义;高、中剂量BoxA干预组大鼠p-NFκB-p65表达水平较EP组明显降低(P<0.05),而低剂量BoxA干预组与EP组间差异未显示统计学意义。结论:HMGB1拮抗剂BoxA可通过抑制NFκB活化,降低大鼠的癫痫易感性,减轻脑组织损伤,具有一定脑保护作用。
Objective：To investigate the effects of high mobility group box 1（HMGB1） antagonist BoxA on seizure onset and hippocampus injury in a rat epilepsy model. Methods：Male SD rats were divided into the sham operation group,the epilepsy model group,the low,middle and high doses of BoxA pretreated epilepsy groups. The rat epilepsy model was made by micro-injection of kainic acid into the hippocampus. Various doses of BoxA were administered to the epilepsy model by intracerebroventricular injection prior to kainic acid injection. The sham operation group were injected with the same volume of normal saline into the hippocampus and lateral ventricle,respectively. We observed the rats＇ behavior during seizure and recorded seizure onset time（SOT） to stage Ⅲ as an indicator to assess epileptic susceptibility. The brain pathological change was observed by HE staining. The injury degree of the hippocampus was estimated by NeuN staining as an indicator to assess the damage of brain tissue. The expression of phosphorylated nuclear factor-κB-p65（p-NFκB-p65） was also detected by immunohistochemical staining. Results：SOT in the low,middle and high doses of BoxA pretreated epilepsy group all significantly prolonged compared to the epilepsy group（P〈0.05）. Compared to the epilepsy group,hippocampus injury and neuron loss were obviously reduced in the BoxA pretreated epilepsy group（P〈0.05）.Although pretreatment with high dose BoxA also prolonged SOT and decreased the intensity of brain injury compared to the middle and low dose BoxA,there were no statistically significant differences. The expressions of p-NFκB-p65 in the middle and high dose BoxA groups were reduced remarkably compared with the EP group（P〈0.05）,and there was no statistical difference between the EP group and the low dose BoxA group. Conclusion：Administration of HMGB1 antagonist BoxA to epileptic rats could reduce seizure susceptibility and attenuate the injury of brain by inhibit the activation of NFκB,which showed brain protective effect in epilepsy rats.
出处
《南京医科大学学报（自然科学版）》
CAS
CSCD
北大核心
2014年第7期904-908,共5页
Journal of Nanjing Medical University(Natural Sciences)
基金
国家自然科学基金(81171222)
