惊厥持续状态后大鼠海马TLR4、IL-1β的表达及意义

Expression of TLR4 and IL-1β in hippocampus of rats after status convulsion

目的观察大鼠惊厥持续状态(status convulsion,SC)后海马的病理改变及TLR4、IL-1β的动态表达,阐明免疫反应在惊厥性脑损伤发病机制中的作用。方法 88只SD大鼠分为生理盐水组(A组)、SC组(B组),B组用氯化锂-匹罗卡品法成功制作SC模型后,再分为B1-B4组(分别于惊厥后4、24、48和72h处死)。光镜观察大脑皮层及海马各区形态学改变,电镜确认海马CA1区神经元超微结构变化,RT-PCR检测海马TLR4、IL-1βmRNA的动态表达。结果长程惊厥发作后,大鼠海马神经元的损伤存在动态变化,随着观察时间的延长,72h内病变逐渐加重。TLR4 mRNA于惊厥后4h开始升高(P<0.05),并随时间延长逐步增高,于72h时达到高峰点(P<0.01),而IL-1βmRNA在惊厥后4h即达高峰(P<O.01),此后随时间延长而下降,至72h时已降至正常水平(P<0.05)。结论 TLR4和IL-1β参与了惊厥性脑损伤的发生、发展过程,且IL-1β的早期升高可能对TLR4的生成有间接促进作用。

Objective To observe the changes of neuron pathology and the expression of TLR4 and IL- 1βin hippocam-pus of rats after status convulsion. Methods Eighty eight male Sprague- Dawley （SD） rats were randomly divided into control group （A） and convulsion group （B）. The status convulsion was induced by injection of lithium chloride- pilocarpine in group B, then the animals were sacrificed at 4h, 24h, 48h, 72h after convulsion discontinued （subgroup B1- B4）. The histopathological changes in hippocampus were observed by HE staining and electron microscopy, the expression of TLR4 and IL- 1β mRNA in hippocampus were detected by RT- PCR. Results Neuronal injury was observed in group B by HE staining and electron mi-croscopy, and the changes were increased gradual y at 72h after convulsion, Compared with controls the expression of TLR4 mRNA in rat hippocampus of group B started to increase at 4h （P〈0.05） and reached the peak at 72h after convulsion;while the expression of IL- 1βmRNA reached the peak at 4h （P〈0.01）, then gradual y decreased and returned to normal at 72h after con-vulsion P〉0.05）. Conclusion The expression of TLR4 and IL- 1β may be associated with brain injury in SC rats, and the early increased IL- 1βexpression may promote the expression of TLR4.