迷走神经递质乙酰胆碱(ACh)能够激活α7尼古丁乙酰胆碱受体(α7nAChR)；激活α7nAChR能抑制多因素所致的肝损伤；枯否细胞功能影响肝缺血再灌注 (HIR) 损伤。我们假设"肝迷走神经递质ACh经激活枯否细胞α7nAChR减轻HIR损伤"。利用切除肝迷走神经小鼠、清除枯否细胞小鼠、α7nAChR-/- 小鼠制作HIR模型，分离培养小鼠枯否细胞和肝细胞，拟从以下5个方面进行验证：1)激活α7nAChR减轻HIR损伤；2) α7nAChR-/-加重HIR损伤；3) 肝迷走神经切除加重HIR损伤，预激活α7nAChR阻止这一损伤；4) 清除枯否细胞减轻HIR损伤；5) 枯否细胞α7nAChR介导抗HIR损伤可能机制。该项目试图明确肝迷走神经在抗HIR损伤的作用，并探索枯否细胞α7nAChR作为抗HIR损伤靶点的可能性，从而为临床HIR损伤的预防提供新思路。

The principal neurotransmitter released by the vagus nerve can activate α7 nicotinic acetylcholine receptor (α7nAChR). Activation of α7nAChR inhibits hepatocyte injury under various pathological conditions, including hepatic ischemia-reperfusion (HIR) injury. Kupffer cells (KCs) are likely to be a major determinant influencing HIR injury. We hypothesize that hepatic vagus nerve attenuates ischemia reperfusion induced injury in mouse liver via α7nAChR on KCs. HIR models are prepared by using hepatic vagotomy,KCs eliminated and α7nAChR-/- mice, and primary KCs and hepatocytes are isolated. This work is designed to demonstrate: 1) activation of α7nAChR attenuates HIR injury; 2) α7nAChR-/- aggravates HIR injury; 3) hepatic vagotomy exacerbates HIR injury, which is prevented by pretreatment with selective α7nAChR agonist; 4) removal of KCs diminishes HIR injury; 5) possible mechanisms in HIR injury mediated by α7nAChR on KCs. The expected results are: 1) the hepatic vagus nerve plays an important role during the development of HIR injury through α7nAChR on KCs; 2) α7nAChR on KCs is a potential pharmacological target in resisting against HIR injury. HIR injury is relevant clinically in hepatic surgery and liver transplanation, our results may therefore provide a new strategy for prevention of liver injury during ischemia reperfusion.