Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Scand J Immunol. 2014 Feb;79(2):105-12. doi: 10.1111/sji.12141.
The parasympathetic nervous system has been known to modify innate immune responses. In animal models, acetylcholine (Ach) released from the distal ends of nerves has been shown to inhibit inflammatory responses such as endotoxic shock, pancreatitis, intestinal inflammation, etc. However, its role in LPS-induced fulminant hepatitis remains to be elucidated. Here, we demonstrate that the vagus nerve acts as a suppressor in the liver after challenge with LPS plus D-gal. The vagus nerve acts through the α7 AchR expressed on the surface of Kupffer cells, inhibiting the production of the proinflammatory cytokines TNF and IL-6. A mechanism study revealed that the suppressive effect of Ach may occur through the activation of Src kinase and subsequent inhibition of the Myd88 signal pathway. Our study has suggested a suppressive role of vagus nerve in the modulation of liver inflammatory responses, which should be noticed during clinical massive hepatectomy and liver transplantation. The nicotinic anti-inflammatory pathway may also be a potential target for sepsis after liver transplantation.
副交感神经系统已被证实可以调节先天免疫反应。在动物模型中，从神经末梢释放的乙酰胆碱（Ach）已被证明可以抑制炎症反应，如内毒素休克、胰腺炎、肠道炎症等。然而，其在 LPS 诱导的暴发性肝炎中的作用仍有待阐明。在这里，我们证明了迷走神经在 LPS 加 D-半乳糖攻击后在肝脏中起抑制作用。迷走神经通过在枯否细胞表面表达的α7 AchR 起作用，抑制促炎细胞因子 TNF 和 IL-6 的产生。机制研究表明，Ach 的抑制作用可能通过Src 激酶的激活和随后抑制 Myd88 信号通路而发生。我们的研究表明，迷走神经在调节肝脏炎症反应中起抑制作用，这在临床大量肝切除术和肝移植中应引起注意。烟碱抗炎途径也可能是肝移植后脓毒症的一个潜在靶点。
