乌司他丁对Wistar大鼠暴发性肝衰竭的治疗作用

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

目的研究乌司他丁(Ulinastatin,UTI)对大鼠暴发性肝衰竭(fulminant 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-GalN)、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2×105U/kg,其他两组注射等量生理盐水。于造模后6、12、24、48 h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。

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.