TLR4/NF-κB信号通路调控血管性痴呆小胶质细胞极化以及中医治疗的研究进展

TLR4/NF-κB Signaling Pathway Regulates Microglial Polarization in Vascular Dementia and Research Progress of TCM Treatment

血管性痴呆(vascular dementia,VaD)为临床常见的神经退行性疾病,严重危害人类健康。不管是持续低灌注状态还是重建血流导致的再灌注损伤,大脑中都存在严重的神经性炎症,其中小胶质细胞作为中枢神经系统炎症反应的关键调节因子,在神经元的死亡起着重要的作用,其表型极化的激活传统上被归类为神经毒性M1型或神经保护性M2型,促进小胶质细胞向M2型极化具有明显抗炎作用而改善神经炎症。Toll样受体(toll like receptors TLRS)家族的TLR4在小胶质细胞表面广泛表达,并通过激活下游信号经典炎症蛋白核因子κB(nuclear factor kappa-B)NF-κB参与神经炎症的调节,因此研究TLR4/NF-κB信号通路通过调控小胶质细胞表型极化而抑制神经性炎症具有重要的意义,中医药治疗VaD具有悠久的历史,其疗效显著不良反应小,目前多项研究表明中医药单体、中药复方等通过多靶点治疗的优势,可通过抑制TLR4/NF-κB的激活从而调控小胶质细胞从炎症M1表型到保护性M2表型的早期转变而保护神经元细胞,因而从TLR4/NF-κB信号通路调控VaD小胶质细胞极化的机制研究以及中医药的治疗,以期可为今后VaD的治疗研究提供参考。

Vascular dementia(VaD)is a common clinical neurodegenerative disease that poses a serious risk to human health.Regardless of the persistent hypoperfusion state or reperfusion injury due to reestablished blood flow,there is severe neuroinflammation in the brain.Microglia,as the key regulator of the inflammatory response in the central nervous system,plays an important role in neuronal death,and the activation of their phenotypic polarization is traditionally classified as neurotoxic M1 type or neuroprotective M2 type,promoting microglia polarization to M2 type TLR4 of the Toll like receptors TLRS family is widely expressed on the surface of microglia and is involved in the regulation of neuroinflammation through activation of the downstream signaling classical inflammatory protein nuclear factor kappa-B(NF-κB).Therefore,it is important to study the TLR4/NF-κB signaling pathway to suppress neuroinflammation by regulating microglia phenotypic polarization,and traditional Chinese medicine has a long history of treating this disease with significant efficacy and few side effects.Therefore,this review examined the mechanism of TLR4/NF-κB signaling pathway to regulate microglia polarization in vascular dementia and the treatment of VaD with traditional Chinese medicine,in order to provide a reference for future research on the treatment of VaD.