目的 观察液压冲击脑损伤大鼠Toll样受体蛋白4(TLR4)与炎性细胞因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)表达变化,探讨TLR4对炎性因子的调控作用.方法 成年雄性SD大鼠48只,制作液压冲击颅脑损伤模型,术后6、12、24 h、3、7d断头处死,用干湿重法、免疫织化法分别测定水肿脑组织含水量及其TLR4、IL-1β、IL-6、TNF-α表达.结果 创伤性颅脑损伤(TBI)组大鼠脑含水量从6h开始增加[(78.86 ±0.54)%],24 h时达到最大值[(83.07±0.27)%],持续至3d开始下降[(81.85±1.26)%];免疫组织化学显示水肿脑组织TLR4、IL-1β、IL-6、TNF-α的表达均在6h时开始增高(1.50±0.58、3.75±0.48、3.50±0.58、5.75 ±2.36),在12h或24 h时达到高峰(5.50±1.00、7.80±1.64、7.75±1.05、7.50±1.73),7d后降低.线性相关分析显示TLR4表达与IL-1β、IL-6、TNF-α表达呈正相关(r=0.941、0.907、0.836,P<0.05).结论 大鼠颅脑液压冲击伤TLR4、IL-1β、IL-6、TNF-α均出现高表达,TLR4可能通过调控炎性因子介导继发性脑损伤.
Objective To investigate the expression of Toll-like receptor 4 (TLR4) and inflammatory cytokines such as interleukin (IL)-1β,IL-6 and tumor necrosis factor (TNF)-α,and explore the modulatory effect of TLR4 on inflammatory cytokines following fluid percussion brain injury in rats.Methods The experimental models were established in 48 adult rats.The water content of edematous brain and the expression of TLR4,IL-1β,IL-6 and TNF-α were measured with dry-wet measure,and immunohistochemistry at 6,12,24 h,3 day,and 7 day after operation respectively.Results As compared with shamoperated group,the water content of edematous brain was increased in traumatic brain injury (TBI) group from 6 h [(78.86 ± 0.54) %] to the maximum at 24 h [(83.07 ± 0.27) %],and gradually decreased at 3 day [(81.85 ± 1.26)%].TLR4,IL-6,IL-1β and TNF-α immunoreactive expression was increased from 6 h (1.50 ± 0.58,3.75 ± 0.48,3.50 ± 0.58,and 5.75 ± 2.36 respectively) to the maximum at 12 h or 24 h (5.50 ± 1.00,7.80 ± 1.64,7.75 ± 1.05,and 7.50 ± 1.73 respectively),lasted to the 3rd day,and began to drop at 7th day.The linear regression analysis indicated that TLR4 expression had positive correlations with expression of IL-1 β,IL-6 and TNF-α (r =0.941,r =0.907,r =0.836 respectively,P 〈 0.05).Conclusion TLR4,IL-6,IL-1β and TNF-α expression is upregulated following fluid percussion injury in rats,and TLR4 is involved in secondary brain injury by mediating inflammatory cytokines.