苦参碱对脂多糖/痤疮丙酸杆菌诱导的小鼠肝炎及产生肿瘤坏死因子的影响

用小鼠致死性肝炎模型和TNF体外诱生的方法,研究苦参碱(Mat)对脂多糖(lipopolysaccharides,LPS)诱导的经痤疮丙酸杆菌(propionibacterittm acnes,PA)预刺激的小鼠产生肿瘤坏死因子(TNF)以及致死性肝炎的影响。结果表明:Mat(10,50mg·kg^-1,ip,bid×3d)可降低血清TNF和ALT水平及小鼠对LPS致死毒性的敏感性,并可在体外抑制LPS诱导的经PA预刺激的小鼠腹腔巨噬细胞释放TNF。提示Mat的保肝作用与其抑制TNF释放有关。

EFFECT OF MATRINE ON MOUSE HEPATITIS AND TUMORNECROSIS FACTOR PRODUCTION INDUCED BY PROPIONIBACTERIUM ACNES/ LIPOPOLYSACCHARIDES

The effect of matnne (Mat) on lipopolysaccharides (LPS)-induced fatal hepatitisand tumor necrosis factor (TNF) production in Propionibacterium acnes (PA)-pnmed mice werestudied. Mice were injected ip LPS (10 μg/mouse) 7 d after ip PA (0.5 ml/mouse) to induce fatalhepatitis. Aster ip LPS, serum TNF activity rose to 1657 ± 406 kU. L^-1 at 1.5 h and ALT activityincreased up to 1496 ± 890 U. L^-1 at 5 h. Six of 8 mice died within 5 h and the massive hemorrhagicnecrosis of the liver was observed in all mice. Administration of Mat ( 10, 50 mg.kg -1 , ip, bid × 3 d)before the LPS injection markedly reduced the elevation of serum TNF and ALT activity in a dose-dependent manner, and diminished the mortality induced by LPS. Liver congestion and necrosisinduced by LPS in PA-primed mice were ameliorated markedly by Mat pretreatment. Mat (62.5～250mg. L^-1) inhibited LPS-induced TNF release from PA-primed mouse peritoneal macrophage in vitroin a concentration-dependent manner. These results seggest that Mat protected PA-primed mice fromthe development of fatal hepatitis induced by LPS due to inhibition of TNF production.