Establishment of the hepatic reserve and molecular biological analyses of liver function after hepatectomy

1.已在大鼠中检查了取决于胆管结扎持续时间的有机阴离子（胆汁酸、胆红素）转运蛋白表达的差异。结扎后3 ~ 28天取血及肝组织。排泄转运蛋白mrp 2的mRNA表达从结扎后3天开始下降，mrp 3的mRNA表达从结扎后3天开始上升。摄取转运蛋白ntcp和oatp在结扎后28天开始下降，而mdr 2在结扎后没有变化。我们正在检测这些蛋白质水平的表达。2.在大鼠中检测肝储备功能和预测肝衰竭的参数在扩大肝切除术后早期的差异。我们测定了大鼠70%和90%肝切除后胆汁流量、胆汁酸分泌和胆汁酸转运体mRNA的表达。90%肝切除后胆汁流量和胆汁酸分泌均显著下降，这是一种急性肝功能衰竭模型。90%肝切除后胆汁酸排泄量减少，mrp 2表达降低，mrp 3和bsep表达增加。相反，70%肝切除后mrp 2表达增加，mrp 3和bsep表达下降。mrp 2和mrp 3在70%和90%肝切除后表达有不同程度的调节。我们推测mrp 2和mrp 3的表达可能能够预测扩大肝切除术后的肝功能衰竭。3.我们检测了生长因子、转录因子和细胞周期调节因子在2/3肝切除和门静脉分支结扎后再生反应中的表达。我们报道了大鼠门静脉分支结扎后和肝切除后，细胞周期蛋白D1 mRNA表达在萎缩的肝叶中减少，在增生的肝叶中增加（参考文献1）。我们还报道了大鼠肝缺血再灌注后肝损伤的机制（参考文献2）。

1.The differences in the expression of the organic anion (bile acid, bilirubin) transporters depending on the duration of bile duct ligation have been examined in rats. Blood and liver tisues during the period from 3 to 28 days after the ligation were obtained. The excretion transporters, the mRNA expressions of mrp2 decreased while those of mrp3 increased from 3 days until 28 days after the ligation. The uptake transporters, ntcp and oatp decreased until 28 days after the ligation, while the mdr2 did not change after the ligation. We are now examining the expression of these protein levels.2.The differences in hepatic reserve function and parameters to predict the liver failure in the early stage after extended hepatectomy were examined in rats. We determined the bile flow, biliary bile acid secretion and the mRNA expressions of bile acid transporters after 70 % or 90 % hepatectomy in rats. The bile flow and bile acid secretion both decreased significantly after the 90 % hepatectomy, which is a model for acute liver failure. Biliary bile acid excretion and the expression of mrp2 decreased, while the expressions of mrp3 and bsep increased after 90 % hepatectomy. In contrast, the expression of mrp2 increased, while the expressions of mrp3 and bsep decreased after 70 % hepatectomy. The expressions of mrp2 and mrp3 was differently regulated after 70 % and 90 % hepatectomy. We suspected that expressions of mrp2 and mrp3 might be able to predict the liver failure after extended hepatectomy.3.We examined the expression of growth factors, transcription factors, and cell cycle regulators in response to regeneration after a two-third hepatectomy and portal vein branch ligation. We reported that the mRNA expression of Cyclin D1 decreased in the atrophying and increased in the proliferating lobes after portal vein branch ligation and after hepatectomy in rats (ref.1). We also reported the mechanisms of liver damage after hepatic ischemia and reperfusion in rats (ref.2).