急性肝衰竭大鼠微囊化肝细胞移植后HMGB1的动态变化

目的 本实验将微囊化肝细胞移植人急性肝衰竭大鼠腹腔内,动态观察大鼠肝功能和肝组织中高迁移率族蛋白B1(HMGB1)的表达情况和意义. 方法 用D-氨基半乳糖制作大鼠急性肝衰竭模型,随机分成3组:Ⅰ组为生理盐水组,Ⅱ组为裸肝细胞移植组,Ⅲ组为微囊化肝细胞移植组.在6、12、24、48、72、120和168 h,检测各组血生化,用RT-PCR方法检测肝组织HMGB1 mRNA的表达.另取6只正常大鼠样本作为参考值. 结果 各模型组ALT、AST和TBil在6 h就开始上升,24 h均已显著升高(P＜0.05),Ⅲ组ALT、AST和TBil显著下降,与Ⅰ、Ⅱ组比较差异有统计学意义(P＜0.05或P＜0.01).各模型组HMGB1mRNA在6 h显著升高(P＜0.01),12 h达高峰,Ⅱ组、Ⅲ组在24 h后表达量较Ⅰ组显著下降,72 h、120 h时Ⅲ组与Ⅱ组比较差异有统计学意义(P＜0.01). 结论 HMGB1可能参与了急性肝衰竭的病理生理过程,微囊化肝细胞移植组明显减少了肝衰竭大鼠肝组织中HMGB1 mRNA的表达,从而减轻肝组织炎症反应并改善肝衰竭大鼠的预后.

Dynamic change of HMGB1 in acute liver failure rat after transplantation of microencapsulated hepatocytes

Objective To detect hepatic function and high mobility group box 1(HMGB1)in dynamic state after microencapsulated hepatocytes transplating into rats with acute liver failure(ALF). Methods We made the model of ALF with D-GalN and assigned the models to 3 groups randomly: group Ⅰ were made with NS; group Ⅱ were made with gymno-hepatocyte; group Ⅲ were made with microencapsulated hepatocyte. The changes of hepatic function and HMGB1mRNA were detected by semiquantitative RT-PCR at the time of 6 h, 12 h, 24 h, 48 h, 72 h, 120 h and 168 h.In addition, reference value came from 6 normal rats. Results ALT, AST and total bilirubin(Tbil)began to increase at 6 h in 3 model groups, and increased significantly at the time of 24 h( P ＜ 0.05). ALT, AST and Tbil in group Ⅲ were decreased obviously, and there was statistical significance with group Ⅰ and group Ⅱ ( P ＜ 0.05 or P ＜ 0.01). In 3model groups, the expression of HMGB1 mRNA increased obviously at 6 h( P ＜ 0.01)and reached to peak at 12 h. Compared with group Ⅰ ,the expression of HMGB1 mRNA in groupⅡ and groupⅢ descended significantly after 24 h. There was statistical significance between group Ⅲ and group Ⅱ at 72 h and 120 h( P ＜ 0.01). Conclusions HMGB1 are intimately associated with ALF. Hepatocellular transplantation can decrease the expression of HMGB1 mRNA in hepatic tissue of rats with ALF, reduce the inflammation of the liver and improve the prognosis of ALF rats.