Alcoholic hepatitis (AH) is an important form of alcoholic liver disease (ALD), and its incidence is continuously increasing leading to advanced disease burden. The NOD-like receptors (NLRs) are a specialized group of intracellular pattern recognition receptors, which participate in inflammatory diseases. However, the role of NLRs in the pathogenesis of AH still remain obscure. The animal model of alcoholic hepatitis in mice was established according to National Institute on Alcohol Abuse and Alcoholism (NIAAA) method. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of NLR family members in liver tissues of the ethanol-fed(EtOH-fed)group and pair-fed group. NLRP6 was overexpressed in mice by injecting Recombinant Adeno-Associated Virus into the tail vein. Mouse Cytokines and Chemokines RT² Profiler PCR Array was used to analyze the related cytokines and chemokines involved in the development of alcoholic hepatitis. Among the NLR family members, the expression of NLRP6 decreased most significantly in the animal model of AH. Our results demonstrated that overexpression of NLRP6 in vivo obviously alleviated steatosis, inflammation and fibrosis in liver. Meanwhile, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice also decreased. Besides, Chemokine (C–C motif) ligand 20(CCL20) was one of the most significantly up-regulated chemokines in the mouse AH model and CCL20 was participated in NLRP6-mediated AH. NLRP6 could inhibit the activation of nuclear factor (NF)-κB signaling pathway in vitro and in vivo. Furthermore, the activation, proliferation, and migration of hepatic stellate cells was enhanced after downregulation of NLRP6. In summary, NLRP6 may play a protective role in the development of AH. NLRP6 could inhibit activation of NF-κB signaling pathway in AH.

酒精性肝炎（AH）是酒精性肝病（ALD）的一种重要形式，其发病率不断增加，导致疾病加重。NOD样受体（NLRs）是一组特殊的细胞内模式识别受体，参与炎症性疾病。但是，NLR在AH发病机理中的作用仍然不清楚。根据国家酒精滥用和酒精中毒研究所（NIAAA）的方法建立了小鼠酒精性肝炎的动物模型。实时定量聚合酶链反应（qRT-PCR）用于分析乙醇喂养（EtOH）组和成对喂养组肝组织中NLR家族成员的表达。通过将重组腺相关病毒注入尾静脉，NLRP6在小鼠中过表达。小鼠细胞因子和趋化因子RT²Profiler PCR Array用于分析与酒精性肝炎发展有关的相关细胞因子和趋化因子。在NLR家族成员中，在AH动物模型中NLRP6的表达下降最为明显。我们的结果表明，NLRP6在体内的过度表达明显减轻了肝脏的脂肪变性，炎症和纤维化。同时，小鼠的血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平也降低。此外，趋化因子（CC基序）配体20（CCL20）是小鼠AH模型中最显着上调的趋化因子之一，CCL20参与了NLRP6介导的AH。NLRP6可以在体外和体内抑制核因子（NF）-κB信号通路的激活。此外，激活，扩散，下调NLRP6后，肝星状细胞的迁移得以增强。总之，NLRP6可能在AH的发展中起保护作用。NLRP6可以抑制AH中NF-κB信号通路的激活。