摘要
目的观察特异性激活Toll样受体3(Toll-like receptor 3,TLR3)-Toll/IL-1受体结构域接头分子(Toll/IL-1receptor domain containing adaptor inducing IFN-β,TRIF)信号通路药物聚肌胞苷酸(polyinosinic polycytidylic acid,Poly Ⅰ:C)对局灶性脑缺血损伤小鼠是否有保护作用,并探讨保护作用是否与抑制炎性作用有关。方法对小鼠进行一次性肌肉注射0.3mg/kg Poly Ⅰ:C,24h后进行左侧大脑中动脉栓塞(middle cerebral artery occlusion,MCAO),栓塞2h后进行再灌注6、12、22h,诱导小鼠的脑缺血再灌注损伤模型,TTC染色方法测定脑缺血体积;Western blot方法检测缺血侧脑组织TRIF蛋白表达;ELISA方法检测小鼠缺血侧半脑脑组织炎性因子干扰素-β(interferon-β,IFN-β)、白细胞介素-10(interleukin-10,IL-10)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的含量。结果缺血2h再灌注6、12、22h的小鼠出现明显的神经缺陷症状及脑组织梗死,在缺血再灌注各个时间点,小鼠缺血侧脑组织中IL-6、TNF-α表达均升高。0.3mg/kg Poly I:C能减少梗死面积,改善神经缺陷,提高小鼠缺血侧脑组织TRIF蛋白的表达,能在不同时间点升高IFN-β水平并降低缺血再灌注缺血侧脑组织IL-6和TNF-α的含量。结论 0.3mg/kg Poly Ⅰ:C对脑缺血损伤小鼠有保护作用,保护作用机制与抑制小鼠脑缺血再灌注损伤过程中的炎症反应有关。
Objective To examine the influence of polyinosinic-polycytidylic acid（Poly Ⅰ：C）on focal cerebral ischemia-reperfusion injury through Toll-like receptor 3（TLR3）-Toll/IL-1receptor domain-containing adaptor inducing IFN-β（TRIF）signaling pathway in mice and to explore the effects of Poly Ⅰ：C on the inhibition of inflammatory reaction.Methods Mouse ischemia/reperfusion（I/R）models were established by 2hleft middle cerebral artery occlusion（MCAO）followed by 6,12,22 hreperfusion.Animals were treated with 0.3mg/kg Poly Ⅰ：C via one-time intramuscular injection before MCAO.Cerebral infarct volume was detected by TTC staining;the expression level of TRIF protein in ischemic brain tissues was measured by Western blot,and TNF-α,IL-6,IFN-β,and IL-10 levels by ELISA.Results Two-h left MCAO followed by 6,12,22 hreperfusion could result in severe nerve defects and cerebral infarction.The levels of TNF-αand IL-6were significantly increased in ischemic brain tissues at each I/R time point.Treatment of the mice with Poly I：C（0.3mg/kg）prior to MCAO could reduce cerebral infarct volume,improve the nerve defects,increase TRIF protein expression,enhance the secretion of IFN-β,and down-regulate the levels of TNF-αand IL-6in ischemic brain tissues.Conclusion Poly Ⅰ：C can protect against cerebral ischemia-reperfusion injury by reducing inflammation reaction.
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2015年第5期515-519,共5页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
国家自然科学基金资助项目(No.81001432)
