黄芩素抑制Toll样受体4/核因子-B炎症通路改善小鼠脑出血后脑损伤的作用及机制研究

Baicalein ameliorates intracerebral hemorrhage-induced brain injury in mice through inhibition of TLR4/NF-B inflammatory pathway

目的 探讨黄芩素抑制Toll样受体4(TLR4)/核因子-κB(NF-κB)炎症通路改善小鼠脑出血后脑损伤的作用及机制研究。方法 通过胶原酶注射小鼠右侧基底节区诱导小鼠脑出血,模型模型诱导后小鼠腹腔注射不同剂量黄芩素或者同体积溶剂,并通过神经功能学评分及脑水含量分析其保护作用;通过不同时间点给药(模型诱导后6及12h),评估黄芩素治疗时间窗;对TLR4和NF-κB信号通路的变化、小胶质细胞活化及神经细胞退变(FJC)进行检测。结果 黄芩素可减轻脑出血后脑水含量并改善神经功能学评分,并且模型诱导后6 h开始治疗,仍然有效;黄芩素可减少脑出血后神经细胞变性;黄芩素通过抑制小胶质细胞活化及TLR4/NF-κB通路及其下游促炎因子(TNF-α及IL-1β)的产生发挥抗炎作用。结论 黄芩素在脑出血后通过抗细胞死亡和抗炎作用发挥神经保护作用。

Objective To explore the effect of baicalein on ameliorating intracerebral hemorrhage(ICH)-induced brain injury in mice through inhibition of toll-like receptor 4(TLR4) and nuclear factor-κB(NF-κB) inflammatory pathway.Methods The mouse hemorrhage model was induced by collagenase inj ection into the right basal ganglia region.Baicalein or vehicle were administrated one hour after injury,and the protective effects were analyzed by neurological scores and brain water content.Subsequently,the therapeutic window of baicalein was assessed by administration at different time points(six hours and twelve hours after injury).To further explore possible mechanisms,changes in TLR4/NF-κB signaling pathways,microglia activation and neuronal cell degeneration(FJC) were examined.Results Baicalein reduced brain water content and improved neurological scores after ICH.Delayed treatment with baicalein until six hours after ICH to mice was still neuroprotective.Moreover,baicalein exerted anti-inflammatory effects by inhibiting microglia activation,TLR4/NF-κB pathway and subsequent downstream pro-inflammatory cytokines,such as TNF-α and interleukin-1β(IL-1β).Conclusions Baicalein exerts neuroprotective effects through anti-cell death and anti-inflammatory effects after ICH.