白介素1β单克隆抗体对癫痫致大鼠海马组织炎症反应的影响

The interleukin-1β antibody attenuates epilepsy induced inflammation in rats' hippocampus

目的观察白介素1β(IL-1β)单克隆抗体对氯化锂-匹罗卡品诱导的癫痫大鼠海马组织炎症反应的影响。方法将大鼠随机分为对照组、生理盐水+癫痫模型组(模型组)、IL-1β抗体治疗+癫痫模型组(单抗组),以氯化锂-匹罗卡品建立癫痫动物模型。采用蛋白质印记法检测海马组织中治疗抗体的浓度,RT-PCR检测海马组织中IL-1β、NF-κB mRNA表达水平,酶联免疫吸附法(ELISA)测定血清中S100B水平,免疫荧光法检测海马区胶质细胞活化情况及尼氏染色检测神经元凋亡情况。结果 IL-1β单克隆抗体在海马组织中浓度>3.00μg Ab/g;与模型组比较,治疗组IL-1β、NF-κB表达水平均低于模型组(均P<0.01),血清中S100B蛋白水平明显下降(P<0.01),海马CA3区锥体细胞、神经元缺失情况、胶质细胞活化情况显著减轻(P<0.05)。结论 IL-1β单克隆抗体可能对癫痫导致炎症反应有抑制作用,其机制可能通过中和IL-1β、抑制IL-1β介导炎症信号转导通路而减轻炎症反应,这可能是IL-1β单克隆抗体减轻癫痫所致的神经损伤的机制之一。

Objective To detect the effect of interleukin-1β antibody on rats with epilepsy induced by lithium-pilocarpine. Methods The rats were randomly divided into the sham group,the saline-treated model group（ model group）,and the IL-1β antibody treated model group（ anti-IL-1β group）. Western blot was used to detect the antibody penetration in hippocampus. RT-PCR was used to detect the gene expression of IL-1β and NF-κB mRNA,ELISA was used to detect the serum level of S100 B. Immunological analysis and nissl staining of brain tissue was done to observe the pathological changes of hippocampus. Results The concentrations of IL-1β antibody in hippocampus kept over 3. 00 μg Ab / g. Compared with model group,the mRNA expressions of IL-1β and NF-κB of the IL-1β antibody-treated group was were lower,the serum level of S100 B and the loss of neurons in the IL-1β antibody-treatment group was were also significantly decreased（ P 0. 01）. Additionally repeated systemic administration of IL-1β antibody significantly attenuated the hippocampus glial activation caused by SE（ P 0. 01）. Conclusion The IL-1β antibody could neutralize IL-1β,inhibit IL-1β mediated inflammation and reduce neurological injury caused by epilepsy.