一氧化氮和肿瘤坏死因子在小鼠免疫性肝损伤中的作用及抗肝炎新药SY－801和SY－640的影响

Studies on the Role of Nitric Oxide and Tumor Necrosis Factor in Immunological Liver Injury in Mice and Eftects of New Anti-hepatitis Compounds on the Liver Injury

本研究结果表明：一氧化氮（ＮＯ）在卡介苗（ＢＣＧ）加脂多糖（ＬＰＳ）诱导的免疫性肝损伤中呈现双向作用。来源于吞噬细胞的ＮＯ具有损伤作用，而其它来源的ＮＯ则具有保护作用。肿瘤坏死因子（ＴＮＦ）也参与了ＢＣＧ＋ＬＰＳ诱导的肝损伤。枯否氏细胞通过释放ＮＯ及ＴＮＦ而介导肝损伤。抗肝炎新药ＳＹ－８０１及ＳＹ－６４０的保肝机理与它们升高血浆ＮＯ及降低ＴＮＦ基因表达有关。

An immunological liver injury model was established by injection of micro lipopolysaccharide(LPS )into BCG(bacilli Calmette Guein)-primed mice It was found that nitric oxide(NO)played dual effects in the liver damage induced by BCG+LPS.Thc NO coming from phagocytic cells showed toxic effects while those from the other cells displayed beneficial effects. Tumor necrosis factor(TNF)released by macrophages was also implicated to be a key factor in the liver damage induced by BCG-LPS.Kupffer cells were involved in BCG+LPS-induced liver injury by releasing NO and TNF. The mechanism(s)by which the two new hepatoprotectants(SY-801 and SY-640)reduced BCG+LPSinduced liver damage may be through enhancing mouse plasma NO levels and lowering NO production and TNF expression by macrophages.