AG490对大鼠脑损伤后脑水肿及炎症反应的影响

Effect of AG490 on Brain Edema and Inflammatory Response after Traumatic Brain Injury of Rats

目的研究AG490对大鼠创伤性脑损伤（TBI）后脑组织含水量、CD40表达以及IL-1β,IL-6表达的影响.方法健康雄性SD大鼠120只,随机分为假手术组、TBI＋Saline组和TBI＋AG490组,各组依次分为6h,12h,24h,72h 4个亚组;于规定时间点采用液压冲击法致伤动物,假手术组不予致伤,TBI＋AG490组于伤后1h腹腔注射AG490（5mg/kg）,假手术组和TBI＋Saline组腹腔注射等渗盐水（5ml/kg）;采用干湿重法测定脑组织含水量,流式细胞术检测CD40表达,ELISA法测定IL-1β,IL-6含量.结果脑组织含水量在创伤后显著增高,给予AG490干预后仍呈升高趋势,但与TBI＋Saline组相比明显降低,差异有显著性;CD40,IL-1β,IL-6在创伤发生后表达程度均增高,给予AG490干预可降低其表达水平,与TBI＋Saline组相比差异有显著性.结论创伤性脑损伤后给予AG490能降低受伤脑组织含水量,减轻炎症反应,其机制可能与JAK/STAT途径有关.

Objective To investigate the role of AG490 in regulating the water content of brain tissue and expression of CD40,IL-1βand IL-6 in the injured brain following traumatic brain injury .Methods A total of 120 SD rats were divided into sham group,TBI＋Saline group and TBI ＋AG490 group in random number table.And the rats of the 3 groups were sacrificed at 6h,12h,24h and 72h after injury respectively.After traumatic brain injury（TBI）,the rats were treated by AG490（5mg/kg） using intraperitoneal injection in the TBI ＋AG490 group,and by physiologic saline （5mg/kg） in the sham group and TBI ＋Saline group.The water content of the injured brain was measured by dry-wet weight method.The expression of CD40 was detected by flow cytometry.The expression of IL-1βand IL-6 was detected by ELISA.Results The water content of brain tissue elevated after TBI and achieved the peak 24h after injury,it re-tained high level after 72h.The expression of CD40,IL-1βand IL-6 also elevated after injury.After intervened by AG490,the level of CD40,IL-1β,IL-6 and degree of cerebral edema score declined compared to TBI group （P〈0.05）. Conclusion The degree of cerebral edema and expression of CD 40, IL-1βand IL-6 was depressed remarkably by using AG490 after the traumatic brain injury.The JAK-STAT signal pathway may play an important role in the pathophysiologi-cal process of traumatic brain injury.