乌司他丁对Wistar大鼠暴发性肝衰竭的治疗作用

目的 研究乌司他丁（Ulinastatin，UTI）对大鼠暴发性肝衰竭（fuhninant hepatic failure，FHF）的治疗作用，探讨其作用机制。方法72只Wistar大鼠，随机分为3组：正常组、模型组、治疗组；模型组和治疗组用D-氨基半乳糖（D—GaIN）、脂多糖（LPS）构建大鼠肝衰竭模型，正常组注射等量生理盐水，模型制作成功后治疗组腹腔注射乌司他丁2×10^5U／kg，其他两组注射等量生理盐水。于造模后6、12、24、48h各组分别随机处死6只大鼠，检测血生化指标AST、ALT等，观察肝脏病理变化，测定肝脏髓过氧化物酶（Myelo—peroxidase，MPO）活性，检测血液中TNF—α、IL-1β、IL-6、NO水平。结果与模型组比较，治疗组的存活率升高、生化指标明显好转；病理切片显示，肝脏损伤情况减轻；肝脏MPO活性降低；同时，血清TNF-α、IL-1β、IL-6、NO水平明显降低。结论乌司他丁对大鼠暴发性肝衰竭模型有确切治疗作用，表现为TNF—α等促炎因子的分泌减少，NO炎症损伤减少及炎性细胞浸润降低。

The therapeutical effect of Ulinastatin on fulminant hepatic failure in Wistar rat

Objective To study the therapeutical effects of Ulinastatin （UTI） on fulminant hepatic failure （FHF） in Wistar rat and to investigate its underlying mechanism. Methods Seventy-two Wistar rats were randomly divided into three groups as normal group, model group and treatment group. The model group and trentment group rats were induced into FHF model by D-galactosamine （D-GaIN） and lipopolysaccharide （LPS） intraperitoneal injection, while normal group rats were injected with equal volume normal sodium （ NS）. After model builded, treatment group rats were intraperitoneally injected with Ulinastatin 2 × 10^5 U/kg, while normal group and model group rats were injected with equal volume NS. At each point in time of 6, 12, 24, 48 h, 6 rats were put to death in each group. Plasma ALT, AST etc. were tested, and the mortality, hepatic tissue histology as well as myeloperoxidase （MPO） activity, plasma levels of TNF-α, IL-1β, IL-6, NO were determined. Results Compared with model group, survival rate of treatment group rats rose, plasma ALT, AST decreased, hepatic pathological damage alleviated, and MPO released, and plasma TNF-α, IL-1β, IL-6, NO dilivery reduced obviously. Conclusion The Ulinastatin has definite therapeutical effects on LPS/D-GalN-induced FHF in rat, including reducing proinflammatory factor, alleviating inflammatory cell infiltration.