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

1.大鼠胆管结扎后不同时间有机阴离子(胆汁酸、胆红素)转运蛋白表达的差异。于结扎后3~28d取血和肝组织标本。结扎后3d至28d，排泄转运蛋白mrp2mRNA表达下降，mrp3mRNA表达增加。摄取转运体ntcp和oatp在结扎后28d有所下降，而mdr2在结扎后无明显变化。我们正在检测这些蛋白水平的表达。2.比较大鼠肝脏储备功能和预测早期肝功能衰竭的参数的差异。我们测定了大鼠肝切除70%和90%后胆汁流量、胆汁酸分泌和胆汁酸转运体基因表达的变化。90%肝切除后胆汁流量和胆汁酸分泌均显著减少，是一种急性肝功能衰竭模型。90%肝切除后胆汁中胆汁酸排泄量和mrp2表达减少，mrp3和bsep表达增加。相反，70%肝切除后mrp2表达增加，mrp3和bsep表达降低。70%和90%肝切除后，mrp2和mrp3的表达受到不同程度的调节。我们怀疑mrp2和mrp3的表达可能能够预测扩大肝切除后的肝功能衰竭。3.我们检测了三分之二肝切除和门静脉分支结扎后再生对生长因子、转录因子和细胞周期调节因子的表达的影响。我们报道了大鼠门静脉分支结扎和肝切除后，肝萎缩过程中Cyclin D1mRNA的表达减少，而增殖叶中Cyclin D1mRNA的表达增加。我们还报道了大鼠肝脏缺血再灌注后肝损伤的机制(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).