Natalizumab减轻小鼠创伤性脑损伤炎症反应的作用研究

Effects of Natalizumab in Alleviating Inflammation after Traumatic Brain Injuryin Mice

目的探究Natalizumab在治疗创伤性脑损伤(traumatic brain injury,TBI)炎症反应中的作用。方法对C57BL/6小鼠施以控制性皮质冲击(controlled cortical impact,CCI)以构建TBI小鼠模型;术后3 h小鼠腹腔注射Natalizumab或IgG同型对照抗体,随后在不同时间点对小鼠进行mNSS评分和Morris水迷宫测评;3 d后使用干湿重法评价脑水肿;利用免疫荧光染色观察Natalizumab治疗后小鼠脑组织的免疫细胞浸润情况;利用蛋白质免疫印迹法检测Natalizumab治疗后小鼠脑组织中炎症因子的表达情况。结果TBI小鼠在使用Natalizumab治疗后其mNSS评分显著降低,认知功能改善,脑水肿程度减轻。此外,Natalizumab能抑制T细胞和B细胞在TBI小鼠脑组织中的浸润,并降低炎症因子NOX2和IL-1β的表达。结论Natalizumab能够抑制TBI小鼠的炎症反应并改善其神经功能障碍,有望成为潜在的TBI治疗药物。

Objective To explore the effect of Natalizumab in the treatment of inflammation after traumatic brain injury(TBI).Methods C57BL/6 mice were treated with controlled cortical impact(CCI)to build experimental animal models of TBI.Then 3 h later the mice were intraperitoneally injected with Natalizumab.mNSS score and Morris water maze were performed at different time points after the surgery.Wet-to dry ratio was used to evaluate cerebral edema of mice on day 3.Immune cell infiltration in mice brain tissue after Natalizumab treatment was observed by immunofluorescence staining.Western blotting was used to evaluate the expression of proinflammatory factors in brain tissues of mice.Results After Natalizumab interven-tion,the mNSS score was significantly reduced and TBI-induced cognitive dysfunction was improved in mice.The cerebral edema after TBI in mice was relieved.In addition,T cell and B cell infiltration in mice brain tissues after TBI was significantly reduced.Overexpression of NOX2 and IL-1βin mice brain tissues induced by TBI was also reduced.Conclusion Natalizumab inhibits TBI induced inflammatory response and improves neurological function of mice after TBI.Therefore,Natalizumab may be a potential clinical therapeutic agent for patients with traumatic brain injury.