高迁移率蛋白-1在急性肝衰竭模型猪血清中的变化及意义

Role of the high mobility group box 1 in acute hepatic failure in pig

目的探讨高迁移率蛋白-1(HMGB-1)在急性肝衰竭模型猪血清中的变化,以及人工肝治疗对其影响和意义。方法采用D-氨基半乳糖制备猪肝衰竭模型,随机分为模型组和人工肝治疗组。Westernblot法检测各组动物血清中HMGB-1,用酶联免疫吸附试验检测各组动物肿瘤坏死因子(TNF-α)和白细胞介素1β(IL-1β)水平,并观察人工肝治疗对血清HMGB-1、肝功能和肝组织病理的影响。结果模型组猪血清TNF-α和IL-1β在造模后24h内即达到高峰,后迅速下降;血清HMGB-1在建模后24h开始升高,48h达到高峰,后一直维持较高水平。造模后模型动物肝组织24h出现明显损害,并进行性加重。人工肝治疗组在同期肝损伤较对照组明显减轻,同期血清HMGB-1水平也较对照组明显降低(P<0.05)。结论高迁移率蛋白-1可能参与了急性肝衰竭后期的炎症反应和肝脏病理损伤,人工肝治疗能降低高迁移率蛋白-1在血清中的水平,改善肝脏病理损伤。

Objective To investigate the role of the high mobility group box 1 （ HMGB-1 ） in acute hepatic failure model and the effect of artificial liver support system treatment on HMGB-1 level. Methods Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-or （TNF-α） and interleukin-1β（IL-1β） levels were detected by the enzyme-linked immunosorbent assay （ELISA）, the expression of HMGB-1 was detected by Western blot in different groups. Serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. Results Levels of TNF-α and IL-1β increased and reached a peak at 24 h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB1 started to increase at 24 h in the acute hepatic failure group and reached a peak at 48 h, then kept at a stable high level Significant liver injury appeared at 24 h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB1 was significantly decreased in the group treated with artificial liver support system （P 〈0.05 ）. Conclusions HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure, artificial liver support system treatment may reduce serum HMGB1 level and relieve liver pathological damage.