脂氧素A_4对大鼠急性肝衰竭的保护作用

目的观察脂氧素A4(LXA4)对大鼠急性肝衰竭的保护作用并初步探讨其机制。方法采用D-氨基半乳糖(D-GalN)+脂多糖(LPS)建立大鼠急性肝衰竭动物模型。30只大鼠随机分为四组:正常组、模型组、脂氧素组、四氢化吡咯二硫代氨基甲酸酯(PDTC)组。肝组织病理切片观察肝组织损伤情况;自动生化仪检测肝功能;ELISA法检测血清TNF-α及IL-6水平;免疫组化法检测肝组织核因子κB(NF-κB)表达。结果大鼠急性肝衰竭时,肝组织炎症坏死明显,肝脏转氨酶明显升高,血清IL-6及TNF-α水平显著升高,肝组织NF-κB表达明显增强;脂氧素组及PDTC组组织学改变均明显好转,肝脏转氨酶、细胞因子及NF-κB表达明显下降(与模型组比较,P0.01,);脂氧素组及PDTC组比较,上述指标之间P0.01。结论 LXA4对大鼠急性肝衰竭有明显的保护作用,这种保护作用部分是通过阻断肝组织NF-κB活化,减少促炎细胞因子的释放来实现的。

PROTECTIVE EFFECT OF LIPOXIN A_4 ON ACUTE LIVER FAILURE IN RATS

Objective To observe the protection of lipoxin A4（LXA4） against acute liver failure in rats and to explore its mechanism.Methods The animal model of acute liver failure was produced by intraperitoneal injection with D-galactosamine（D-GalN） plus lipopolysaccharide（LPS）.30 rats were randomly divided into 4 groups：normal,model,LXA4,and PDTC.Pathological changes of liver tissue were detected.The content of TNF-α and IL-6 in the serum was examined by ELISA.The expression of nuclear factor-κB（NF-κB） in liver tissue was detected by immunohistochemical assay.Results In model rats,liver inflammation and necrosis were serious.Liver transaminase,TNF-α and IL-6 in the serum,and NF-κB expression in the liver significantly increased.The above indexes were remarkably reduced in LXA4 and PDTC groups than in the model group（P0.01）,and there were obvious differences between the LXA4 group and PDTC group（P0.01）.Conclusions LXA4 can significantly protect rats against acute liver failure partly by blocking NF-κB activation in liver tissue and reducing the release of pro-inflammatory cytokines.