乌司他丁对GalN/LPS引起大鼠急性肝损伤的保护作用

The protective effect of ulinastatin on GalN/LPS-induced acute liver injury in rats

目的观察乌司他丁(UTI)对D-氨基半乳糖(D-GalN)/脂多糖(LPS)引起大鼠急性肝损伤的保护作用,探讨其作用机制。方法72只SD雄性大鼠进行随机对照分组实验,分为正常对照组、模型组和UTI处理组,各组再分为6h、12h、24h、48h取材4个亚组。腹腔内注射D-GalN/LPS建立大鼠急性肝损伤模型,UTI处理组则在腹腔内注射D-GalN/LPS后立即注射UTI。在相应时间点,门静脉采血检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肿瘤坏死因子α(TNF-α)、一氧化氮(NO)水平;肝组织切片观察肝脏病理形态学变化;测定肝组织丙二醛(MDA)含量,Caspase-3和Caspase-8活性。结果与模型组相比,UTI处理组血清ALT、AST水平在12h、24h和48h组均明显降低(P<0.01);UTI处理组TNF-α、NO水平则在6h和12h有明显降低(P<0.01或0.05);UTI处理组肝组织MDA含量在12h、24h和48h明显降低(P<0.01);UTI处理组处理6h后Caspase-3和Caspase-8活性明显降低(P<0.01)。结论UTI对GalN/LPS引起大鼠急性肝损伤有保护作用,主要通过其抗炎、抗氧化和抗凋亡作用。

Objective To study the effect of ulinastatin （UTI） on GalN/LPS-induced acute liver injury in rats and to investigate its mechanism of action. Methods Seventy-two male SD rats were randomly divided into normal control group, model group and UTI treatment group. Every group was divided into four subgroups： 6, 12, 24, and 48 hours groups with 6 rats in each group. Acute liver injury were induced in the model group and UTI treatment group rats by in- traperitoneal injection of D-galactosamine （D-GalN） and lipopolysaecharide （LPS）. After model establishment, UTI was immediately administered by intraperitoneal injections in the UTI treatment group. Blood samples were collected from the portal vein to detect the contents of serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, tumor necrosis factor （TNF）-α, nitric oxide （NO）. Livers were dissected for measurements of Caspase-3 activity, Caspase-8 activity, MDA content, and histological changes. Results UTI significantly attenuated GalN/LPS-induced increase in serum ALT, AST activity and TNF-ct, as well as NO concentration. Compared with model group, the levels of ALT and AST in UTI treatment group had statistical significance at 12, 24, and 48 hours （P 〈0.01 ）. The levels of TNF-α and NO in UTI treatment group had statistical significance at 6 and 12 hours （P 〈 0.01 or 0.05）. Compared with model group, Caspase-3 activity and Caspase-8 activity in UTI treatment group were decreased obviously at 6 hours （ P 〈 0.01 ）, and the levels of MDA in UTI treatment group were decreased obviously at 12, 24, 48 hours （P 〈 0.01 ）. Conclusion UTI attenuates GalN/LPS-induced acute liver injury via its anti-inflammatory, anti-oxidant, and anti-apoptotic effects.