大量饮酒常会引起显著的肝脏损伤,包括肝脏炎症、纤维化、肝硬化,甚至肝癌.美他多辛被认为是治疗酒精性肝损伤(ALD)的有效药物,可以通过加速酒精代谢和排泄发挥肝脏保护作用,但具体保护机制仍不明确.本研究中,我们给大鼠以5 g/kg的剂量灌胃50％的酒精建立急性酒精性肝损伤模型,收集大鼠血清及肝组织样本,观察肝脏炎症及炎症细胞的浸润程度,以研究美他多辛抑制肝脏炎症的具体作用机制.研究发现,美他多辛可显著缓解ALD大鼠血清ALT、AST、ALP以及炎症因子TNF-a和IL-6水平的升高,并可显著降低肝组织中NLRP3炎症小体的表达,进一步研究发现,美他多辛可显著抑制ALD大鼠肝组织中巨噬细胞和中性粒细胞的浸润程度.研究结果显示,美他多辛可通过抑制酒精损伤诱导的巨噬细胞和中性粒细胞向受损肝脏的浸润,抑制肝脏促炎环境,降低促炎因子分泌,继而发挥肝脏保护作用.“,”Alcohol consumption causes significant liver damage,including hepatitis,fibrosis,cirrhosis,and even primary liver carcinoma.Metadoxine(MTDX)is considered to be a beneficial treatment for alcoholic liver disease(ALD)because it accelerates the metabolism and elimination of ethanol.However,the underlying mechanism is not well understood.Here,the rat model of ALD was developed by feeding with 50％ethanol at the dose of 5 g/kg,and samples of serum and liver tissue were collected to test the levels of liver injury and inflammation and evaluate the hepatoprotective function of MTDX in alcohol-induced liver injury.Further investigation on the infiltration of immune cells was performed to understand the potential hepatoprotective mechanism of MTDX in the ALD model.The results showed that MTDX attenuated liver injury,evidenced by decreased levels of alanine transaminase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP).Meanwhile,the liver proinflammatory environment was improved after MTDX treatment,evidenced by decreased levels of TNF-α,IL-6,and NLRP3 in the liver tissue.Furthermore,inhibited infiltrations of macrophages and neutrophils were observed in MTDX-treated ALD rats compared with the untreated ALD rats.Our results indicated that MTDX played an important role in preventing the progression of ALD,and the underlying mechanisms might be related to its function of attenuating liver inflammation by inhibiting immune cell infiltration.