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

肝切除术后肝储备的建立和肝功能的分子生物学分析。

基本信息

批准号：
17591417
负责人：
CHIJIIWA Kazuo
金额：
$ 2.39万
依托单位：
University of Miyazaki
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591417/
关键词：
obstructive jaundice hepatectomy liver failure bile acid transporter portal vein ligation 閉塞性黄疽

项目摘要

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 tissues 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. After biliary drainage, the change in expression of these mRNA and protein levels are now examined.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 … More significantly after the 90 % hepatectomy, which is a model for acute liver failure (ref.3). 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 Dl decreased in the atrophying and increased in the proliferating lobes after portal vein branch ligation and after hepatectomy in rats. We also reported the mechanisms of liver damage after hepatic ischemia and reperfusion in rats (ref.4). Less

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。取结扎后3~28d的血和肝组织。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。胆汁引流后，检测这些基因表达水平的变化。比较大鼠肝切除后早期肝储备功能和预测肝功能衰竭指标的差异。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。胆汁流量和胆汁酸分泌均降低…更显著的是在90%肝切除后，这是一个急性肝衰竭的模型(参考文献3)。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术后的肝功能衰竭。我们检测了三分之二肝切除和门静脉分支结扎后再生时生长因子、转录因子和细胞周期调节因子的表达。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D1mRNA在肝萎缩过程中的表达减少，而在增殖叶中的表达增加。我们还报道了大鼠肝脏缺血再灌注损伤的机制(参考文献4)。较少