IL-33对大鼠颅脑创伤后认知障碍的初步研究

Preliminary study of IL-33 on cognitive dysfunction after craniocerebral trauma in rats

目的探索白细胞介素33(IL-33)对大鼠颅脑创伤(TBI)后认知功能障碍的影响及其可能的作用机制。方法48只健康雄性SD大鼠随机均分为假手术组(sham组)、TBI组和TBI+IL-33组3组,每组16只。TBI组大鼠颅骨开骨窗后打击皮质,sham组仅开骨窗,TBI+IL-33组造模成功后立即给予IL-33尾静脉注射200ng/只/d,连续3d,其余两组分别注射等量晶体液。3 d后每组大鼠随机取8只大鼠,Western blot法检测海马组织IL-33、白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的水平,荧光TUNEL检测细胞凋亡。另外8只大鼠在1个月后,Morris水迷宫法评估大鼠的记忆能力,并检测海马组织β淀粉样蛋白(Aβ1-42)、tau相对蛋白水平。结果与sham组大鼠相比,TBI组大鼠海马组织中IL-33、IL-1β、TNF-α、Aβ1-42、tau相对蛋白水平、TUNEL细胞阳性率和逃避潜伏期明显升高,而目标象限停留时间和穿越平台次数明显减少,差异均有统计学意义(P<0.05);与TBI组相比,TBI+IL-33组大鼠海马组织中IL-33相对蛋白水平、目标象限停留时间和穿越平台次数升高,差异均有统计学意义(P<0.05),而IL-1β、TNF-α、Aβ1-42、tau相对蛋白水平、TUNEL细胞阳性率和逃避潜伏期均明显减少,差异均具有统计学意义(P<0.05)。结论IL-33治疗可以提高TBI大鼠记忆功能,改善认知功能障碍,这可能与抑制TBI介导的神经细胞炎症、凋亡以及减少Aβ1-42和tau的表达有关。

Objective To explore the effect of interleukin-33(IL-33)on cognitive impairment after Traumatic brain injury(TBI)in rats and its possible mechanism.Methods 48 healthy male SD rats were randomly divided into sham operation group(sham group),TBI group and TBI+IL-33 group,with 16 rats in each group.In TBI group,the cortex was hit after opening the bone window,while in sham group,only the bone window was opened.In the TBI+IL-33 group,IL-33 was injected into tail vein at 200 ng/animal/day for 3 days,and the other two groups were injected with the same amount of vehicle solution.Three days later,eight rats in each group were randomly selected.The levels of IL-33,IL-1βand TNFαin brain tissue were detected by Western blot,and apoptosis was detected by fluorescence TUNEL.In another 8 rats,after 1 month,the Morris water maze was used to evaluate the memory ability of the rats,and the relative protein levels of amyloidβ(Aβ1-42)and tau in the hippocampus were measured.Results Compared with sham group rats,relative protein levels of IL-33,IL-1β,TNF-α,Aβ1-42,tau,positive rate of TUNEL cells and evasive latency were significantly increased in the hippocampal tissues of the TBI group rats,while residence time in the target quadrant and frequency of crossing the platform were significantly decreased(P<0.05).Compared with the TBI group,the levels of IL-33 relative protein,residence time in the target quadrant and frequency of crossing the platform in the hippocampus of rats in the TBI+IL-33 group were increased,and the differences were statistically significant(P<0.05),while the positive rates of IL-1β,TNF-α,Aβ1-42,tau relative protein levels,TUNEL positive cell and escape latency were significantly decreased,and the differences were statistically significant(P<0.05).Conclusion IL-33 treatment can improve the memory function and improve the cognitive dysfunction in TBI rats,which may be related to the inhibition of TBI-mediated nerve cell inflammation and apoptosis,as well as the reduction of expression of tau and Aβ1-42.