摘要
神经胶质细胞激活在神经病理性疼痛(NP)发生和维持中发挥重要作用。Toll样受体4(TLR4)通过激活中枢神经系统胶质细胞(主要是小胶质细胞),诱导促炎因子、神经活性物质等的释放,参与NP的形成和维持及阿片类药物的不良反应,已成为潜在的NP治疗靶标。靶向抑制TLR4的生物学效应在NP模型中已取得初步疗效,其中TLR4信号通路抑制剂—异丁司特已进入Ⅱ期临床试验。本文主要综述TLR4的结构、功能、作用机制、靶向药物研发现状等。
Activation of microglia plays a vital role in the initiation and maintenance of specific neuropathic pain states.By activating microglia in central nervous system,Toll-like receptor 4（TLR4） can promote the release of proinflammatory cytokines and neuroactive compounds,participate in the initiation and maintenance of neuropathic pain,and trigger the opiate side effects.Therefore,TLR4 may be a potential therapeutic target for neuropathic pain.Inhibition of TLR4 has shown some biological effects in neuropathic pain models and ibudilast（the TLR4 pathway-inhibiting agent） has been approved for for phase Ⅱ clinical trials.This article briefly reviews the structure,function,and mechanism of TLR4 as well as the development of TLR4-targeted drugs.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2012年第2期168-173,共6页
Acta Academiae Medicinae Sinicae
基金
国家自然科学基金(30901403
81101906)~~
