目的：探讨活化胆碱能抗炎通路对非酒精性脂肪性肝炎（nonalcoholic steatohepatitis，NASH）模型小鼠肝脏炎症的抑制作用及其分子机制。方法：60只雄性6周龄的无特定病原体（specific pathogen free，SPF）级C57BL/6J小鼠被随机分为4组：正常饮食小鼠生理盐水注射组、正常饮食小鼠尼古丁注射组、NASH模型小鼠生理盐水注射组和NASH模型小鼠尼古丁注射组，分别给予普通饮食及高脂饮食加高果糖饮水，喂养17周后建立NASH小鼠模型，然后予各组小鼠生理盐水或尼古丁腹腔注射，每天1次，注射量为400 μg/kg，注射3周。3周后处死动物进行肝组织病理检查，取小鼠血清行酶联免疫吸附测定（enzyme linked immunosorbent assay，ELISA）检测炎症因子白细胞介素-6（interleukin-6，IL-6）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α），同时原代分离培养肝巨噬细胞，使用Western blot和荧光共聚焦显微镜检测α7尼古丁型乙酰胆碱能受体（alpha 7 nicotinic acetylcholine receptors，α7nAChR）、Toll样受体-4（Toll-like receptors-4，TLR-4）和磷酸化核转录因子-κB（nuclear factor κB of phosphorylation，p-NF-κB）的蛋白水平。结果：成功建立了NASH小鼠模型。给予小鼠尼古丁治疗后，小鼠肝组织病理结果显示，小鼠肝脏炎症和脂肪变性明显减轻；ELISA结果显示，小鼠血清中炎症因子IL-6、TNF-α水平下降；Western blot和荧光共聚焦显微镜结果显示，尼古丁治疗组小鼠α7nAChR蛋白水平上调，p-NF-κB水平下调。结论：活化胆碱能抗炎通路可以通过抑制NF-κB通路减轻NASH小鼠的肝脏炎症。

Objective：To investigate the anti-inflammation effects by activation of the cholinergic anti-inflammatory pathway and its mechanisms in non-alcoholic steatohepatitis (NASH) model mice. Me-thods: 6-week-old male C57BL/6J (B6) mice were randomly divided into four groups: the first group was normal mice, injected with saline; the second group was normal mice, injected with nicotine; the third group was NASH model mice, injected with saline; the fourth group was NASH model mice, injected with nicotine. The experimental mice were fed with either standard chow (SC) or high-fat and high-fructose (HFHF) for 17 weeks to generate an NASH model mice. The mice received injection once daily for 3 weeks ［nicotine dose, 400 μg/kg］. Then, their pathological characteristics and function of the liver were assessed. The expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were analyzed by enzyme linked immunosorbent assay (ELISA). The expressions of alpha 7 nicotinic acetylcholine receptors (α7nAChR), Toll-like receptors-4 (TLR-4) and nuclear factor κB of phosphory-lation (p-NF-κB) in Kupffer cells were determined by Western blot and immunofluorescence assays. Results: We successfully generated NASH model mice by imitating the high-fat and high-fructose dietary style of NASH patients. The results of our investigation demonstrated that nicotine could reduce significantly the levels of IL-6, and TNF-α in serum (P<0.05). The expression of p-NF-κB protein in the group which was NASH model mice injected with nicotine declined significantly as compared with the group which was NASH model mice injected with saline (P<0.05). And the expression of α7nAChR protein elevated significantly conversely (P<0.05). Conclusion: Activation of the cholinergic anti-inflammatory pathway could inhibit the release of inflammatory factors as TNF-α and IL-6 in NASH model mice, and the mechanism for the inhibition of inflammatory was mediated by NF-κB pathway.