α7烟碱型乙酰胆碱受体在胆碱能抗炎通路中的作用机制及应用现状

Mechanism and Application of α7 nAChR in Cholinergic Anti-inflammatory Pathway

胆碱能抗炎通路是一条神经-免疫调节通路,以中枢神经系统的迷走神经为起点,以神经递质乙酰胆碱为基础,以免疫细胞膜表面的α7烟碱型乙酰胆碱受体(α7 nicotinic acetylcholine receptor,α7 nAChR)为关键作用位点。其中,电信号与化学信号相互转化,激活JAK-STAT3、PI3K-Akt等信号通路,抑制NF-κB的核转位,进而抑制促炎因子的释放,促进抑炎因子的释放,调节和控制机体的炎症,具体的作用机制正在研究中。研究表明,可以通过使用药物激活α7 nAChR和电刺激迷走神经这2种方法,激活胆碱能抗炎通路。其中,激活α7 nAChR具有操作简便、创伤小和效果显著等优势。常用药物有选择性激动剂,例如PNU282987和GTS-21等,非选择性激动剂例如烟碱。多项研究显示,该方法在脓毒症、缺血再灌注、胃肠炎、骨关节炎和自身免疫病等外周器官炎性疾病治疗中都具有一定的效果。α7 nAChR作为胆碱能抗炎通路的关键作用位点,成为许多炎性疾病的潜在治疗靶点,本文对胆碱能抗炎通路中的α7 nAChR所涉及的抗炎机制、通路激活方式,以及其近年来在炎性疾病中的应用进行了综述,为未来研究其具体作用机制和新的治疗靶点提供参考。

Cholinergic anti-inflammatory pathway in which acetylcholine released as the neurotransmitter,plays an important role in nerve-immune regulation.In this pathway,with the vagus nerve in the central nervous system as a starting point,the alpha 7 nicotinic acetylcholine receptor(α7 nAChR) on the surface of immune cell membrane is the key functional part.The interaction between electrical and chemical signals regulates the inflammation in the body via modulation of the JAK-STAT3,PI3 K-Akt and other signaling pathways and the nuclear translocation of NF-κB,leading to inhibition of the release of pro-inflammatory factors and promotion of the release of anti-inflammatory factors.However,the detailed mechanism is far from clear.Studies have shown that the cholinergic anti-inflammatory pathway can be activated by drug targeting α7 nAChR and electrical stimulation of vagus nerve.Activation of α7 nAChR has the advantages of simple operation,less damage and significant effect.The commonly used drugs are selective agonists such as PNU282987 and GTS-21,and non-selective agonists such as nicotine.And this method has been found to play a role in the treatment of peripheral organ inflammatory diseases such as sepsis,ischemia-reperfusion injury,gastroenteritis,osteoarthritis and autoimmune diseases.As a key factor in the cholinergic anti-inflammatory pathways,α7 nAChR has become a potential therapeutic target for many inflammatory diseases.This paper reviewed the anti-inflammatory mechanism and activation mode of α7 nAChR involved in cholinergic anti-inflammatory pathway,as well as its application in inflammatory diseases in recent years,which may provide a reference for future research on its detailed mechanism of action and potential application as a new therapeutic target.