褪黑素抑制一氧化氮生成在小鼠免疫性肝损伤中的意义

Role of the inhibitory effect of melatonin on nitric oxide production in immunological liver injury in mice

目的探讨褪黑素（ＭＴ）抑制一氧化氮生成与保护免疫性肝损伤的关系。方法用短小棒状杆菌和脂多糖诱导小鼠免疫性肝损伤模型；分离、培养肝细胞和腹腔巨噬细胞；检测一氧化氮（ＮＯ）、丙氨酸氨基转换酶（ＡＬＴ）、丙二醛（ＭＤＡ）和谷胱甘肽过氧化酶（ＧＳＨｐｘ）变化。结果ＭＴ在０１～１０ｍｇ·ｋｇ－１·ｄ－１浓度范围内，明显降低小鼠免疫性肝损伤中ＭＬＴ和ＭＤＡ水平，部分恢复ＧＳＨｐｘ活性（Ｐ＜００５～００１），同时血浆ＮＯ水平下降（Ｐ＜００５）。左旋单甲基精氨酸则在显著降低血浆ＮＯ水平（Ｐ＜００１）同时，肝损伤征象加重。体外用ＭＴ对肝细胞和巨噬细胞无明显影响。结论褪黑素抑制体内ＮＯ过度生成，有利于保护免疫性肝损伤。

AIM To evaluate the relationship between the inhibitory effect on nitric oxide production and the protective effect of melatonin on immunological liver injury in mice. METHODS An immunological liver injury model was induced by administration of lipopolysaccharide following injection of corynebacterium parvum into mice. Mouse hepatocytes and peritoneal macrophages were isolated and cultured. The effects of melatonin were observed by changes of alanine aminotransferase(ALT), nitric oxide(NO), molondiadehyde(MDA) and glutathione peroxidase(GSH px). RESULTS Melatonin (given at 0 1 mg and 1 0 mg·kg -1 ) inhibited the elevation of NO level( P <0 05), reduced ALT and MDA levels and partially restored GSH px activity( P <0 05～0 01) in liver damaged to mice. In contrast, GN monomethyl L arginine remarkably reduced the elevated plasma NO ( P <0 01) while induced more pronounced liver damage. In addition, the effect of meatonin was not seen in cocultured hepatocytes and macrophages in vitro . Conclusion Melatonin was shown to be a modestly potent inhibitor or nitric oxide production, which might benefit its protective action against immunological liver injury in mice.