目的 探討還原型谷胱甘肽片對酒精性脂肪肝（AFLD）斑馬魚模型的保肝功效。方法 選取黑色素等位基因突變型（albino）品系斑馬魚，分別水溶給予還原型谷胱甘肽片500、1 000、2 000、4 000、8 000 μmol/L，同時設置對照組和模型組，除對照組外，利用2%無水乙醇誘導斑馬魚32 h建立AFLD模型，觀察記錄斑馬魚的死亡情況及表型，確定還原型谷胱甘肽片的最大耐受濃度（MTC）。黑色素等位基因突變型（albino）品系斑馬魚分別給予還原型谷胱甘肽片500、1 000、2 000 μmol/L和陽性對照藥RU-21 100 μg/mL，同時設置對照組和模型組，除對照組外建立AFLD模型，采用油紅O染色觀察斑馬魚肝臟脂肪染色強度（S），計算還原型谷胱甘肽片的保肝功效；H&E染色觀察斑馬魚肝臟病理學改變；實時熒光定量PCR（qRT-PCR）檢測白細胞介素（IL）-6、高遷移率族蛋白1b（HMGB-1b）和腫瘤壞死因子（TNF）-α mRNA表達。結果 還原型谷胱甘肽片對AFLD模型斑馬魚的MTC為2 000 μmol/L。與對照組比較，模型組S顯著增加（P<0.001）；與模型組比較，還原型谷胱甘肽片1 000、2 000 μmol/L組和RU-21組S顯著降低（P<0.01、0.001）；還原型谷胱甘肽片500、1 000、2 000 μmol/L和RU-21 100 μg/mL組保肝功效分別為14%、32%、71%和48%。還原型谷胱甘肽片2 000 μmol/L組肝細胞結構正常，脂肪空泡較模型組減少。與對照組比較，模型組IL-6、HMGB-1b和TNF-α mRNA表達顯著增加（P<0.05、0.01）；與模型組比較，還原型谷胱甘肽片500、1 000、2 000 μmol/L組IL-6、HMGB-1b和TNF-α mRNA表達顯著降低（P<0.01、0.001）。結論 還原型谷胱甘肽片對AFLD具有明顯的保肝作用，其機制與下調IL-6、HMGB-1b和TNF-α表達有關。

Objective To investigate the effect and mechanism of glutathione tablets against alcoholic fatty liver disease (AFLD) by constructing a zebrafish model of AFLD. Methods Zebrafish with albino allele mutation were treated with Glutathione Tablets (500, 1 000, 2 000, 4 000 and 8 000 μmol/L) in water solution respectively. Meanwhile, the control group and model group were set up. Except for control group, zebrafish were induced with 2% absolute ethanol for 32 h to establish AFLD model. The mortality and phenotype of zebrafish were observed and recorded. The maximum tolerable concentration (MTC) of Glutathione Tablets was determined. Albino zebrafish were treated with reduced Glutathione Tablets 500, 1 000 and 2 000 μmol/L and positive control drug RU-21 100 μg/mL respectively. The control group and model group were set up at the same time. Except the control group, the AFLD model was established. The liver fat staining intensity (S) of zebrafish was observed by oil red O staining, and the liver protective effect of Glutathione Tablets was calculated; The pathological changes of zebrafish liver were observed by HE staining; Real time fluorescent quantitative PCR (qRT-PCR) was used to detect IL-6, HMGB-1b and TNF-α mRNA expression. Results The MTC of Glutathione Tablets to zebrafish was 2 000 μmol/L. Compared with the control group, S in the model group increased significantly (P < 0.001); Compared with the model group, S of Glutathione Tablets 1 000, 2 000 μmol/L group and RU-21 group were significantly lower (P < 0.01, 0.001); The hepatoprotective effects of Glutathione Tablets 500, 1 000, 2 000 μmol/L and RU-21 100 μg/mL were 14%, 32%, 71% and 48%, respectively. Compared with model group, Glutathione Tablets 2 000 μmol/L group had normal hepatocyte structure and less fat vacuoles. Compared with control group, IL-6, HMGB-1b and TNF-α mRNA expression in model group were significantly higher (P < 0.05, 0.01). Compared with model group, the levels of IL-6, HMGB-1b and TNF-α in Glutathione Tablets 500, 1 000, 2 000 μmol/L group were significantly decreased (P < 0.01, 0.001). Conclusion Glutathione Tablets had obvious protective effect on AFLD, and the mechanism was related to the obvious down-regulation of inflammatory genes such as IL-6, HMGB-1b and TNF-α.

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南通市科技局項目（JCZ20170）；南通市青年課題A項目（QA2019022）；南通市青年課題（QA2019024）