IL-18和caspase-1在大鼠急性肝衰竭模型中表达及其意义

Expression of IL-18 and caspase-1 in a rat model of acute liver failure and its significance

目的了解IL-18与caspase1在大鼠急性肝功能衰竭的可能作用和机制。方法模型组(n=50)D-氨基半乳糖(D-GalN)/脂多糖(LPS)诱导大鼠急性肝衰竭模型。对照组(n=10)以生理盐水代替药物。于不同时间点对大鼠血清和肝脏组织进行HE和TUNEL染色观察,并对血清ALT、AST和TBIL,IL-18 mRNA和caspase-1蛋白进行检测。结果HE结果提示模型成功。经D-GalN/LPS处理后,模型组大鼠血清ALT、AST和TBIL水平较正常对照组明显升高(P<0.01),且随着时间的延长浓度有升高趋势(P<0.05)。与对照组相比,模型组大鼠肝细胞凋亡指数较正常对照组明显升高,且与时间相关。IL-18 mRNA表达与caspase-1趋势相同,即模型组含量显著高于对照组(P<0.05),且其表达呈时间依赖趋势。结论 IL-18与其活化酶caspase-1在大鼠急性肝功能衰竭中表达升高,且呈相似趋势,提示二者在肝衰竭的发病过程中可能有重要作用。IL-18可望成为急性肝衰竭的预测因子和未来的治疗靶点。

Objective To investigate the potential role and mechanism of IL-18 and caspase-1 in rats with acute liver failure.Methods D-GalN/LPS were applied to inducing the rat model of acute liver failure.Fifty male Wistar rats were randomly divided into 5 groups including 4 model groups and a control group.Rats in the model groups were sacrificed at different time points after the model were set up（10 h,18 h,24 h and 36 h respectively,n=10）,while rats in the control group were treated with normal saline（n=10）.The HE and TUNEL staining for liver tissues were performed,and serum ALT,AST,TBIL,IL-18 mRNA and caspase-1 protein were also examined.Results HE staining suggested that the rat model of acute liver failure was successfully established.The serum ALT,AST and TBIL levels increased significantly in the model groups than in the control group（P0.01）,and the increase presented in a time-dependent manner（P0.05）.The apoptosis index in the model groups was significantly higher than that in the control group,and the increase was also time-dependent（P0.05）.IL-18 mRNA and caspase-1 expression both increased in the model groups as compared with the control group,and the increase was time-dependent（P0.05）.Conclusion The increased expression of IL-18 and caspase-1 in acute liver failure suggests their possible roles in the pathogenesis of liver failure.IL-18 may be used as a potential predictor and a therapeutic target of acute liver failure in the future.