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Study for the renmant liver dysfunciton after extensive hapatectomy using isolated hepatocytes

离体肝细胞大范围肝切除术后残余肝功能障碍的研究

基本信息

批准号：
05671060
负责人：
KAWARADA Yoshifumi
金额：
$ 1.41万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

In in vivo experiment, we have reported that the levels of TxB_2 and 6-KF in peripheral blood increased after extensive hepatectomy, especially in cases with liver failure and that the adminisitration of TxA_2 inhibitor or PGI_2 analog improved the remnant liver funcition and the survival rate. Then we undertook to clarify the cause of liver injury after extensive hepatectomy and to evaluate the effects of TxA_2 inhibitor and PGI_2 analog for the liver, using isolated cells. (Methods) Using mongrel dogs, hepatocytes and Kuppfer cells were isolated after 84% hepatectomy and cultured in the presence of TxA_2 analog (STA_2) , TxA_2 inhibitor (OKY-046) or PGI_2 analog (OP-2507) and then we evaluated the degree of hepatocyte damage. Moreover, we evaluated the indirect effects of these drugs using the co-culture system with these cells. (Results) STA_2 has a cytotoxic effect on hepatocytes isolated after extensive hepatectomy, injuring the plasma membrane and the mitochondria, while OP-2507 … More has a cytoprotective effect on these cells, inhibiting these change. And OP-2507 has an ability to inhibit the TxA_2 production by Kuppfer cells. Though OKY-046 has no direct effect on hepatocytes, it has a ability to inhibit the TxA_2 production by Kuppfer cells. It was showed in the experiment with co-culture system that both of OP-2507 and OKY-046 have cytoprotective effects on hepatocytes. We concluded that OP-2507 has both direct and indirect effect, while OKY-046 has a indirect effect. Our previous in vivo experiment revealed the increase of the levels TxB_2 in portal blood. We were interested in the role of portal organs, especially of the spleen. Then splenic macrophages were isoloated and the evaluation of the capacity of TxA_2 production by these cells. It revealed the increase of TxA_2 production by the cells isolated after extensive hepatectomy and the inhibitory effect of OKY-046 on the TxA_2 production by the cells. We conclude that OKY-046 has a inhibitory effect of the TxA_2 production not only by Kuppfer cellls but also by splenic macrophages. Now, we are trying to clarify the role of intestine after extensive hepatectomy and the cause of liver injury in obstructive jaundice, using simillar cellbiological method. Less

在体内实验中，我们报道了广泛肝切除术后外周血中TxB_2和6-KF水平升高，尤其在肝功能衰竭的病例中，应用TxA_2抑制剂或PGI_2类似物可改善残肝功能，提高存活率。本研究采用离体细胞培养技术，探讨了大面积肝切除术后肝损伤的原因，并评价了TxA_2抑制剂和PGI_2类似物对肝损伤的影响。（方法）杂种犬84%肝切除后，分离肝细胞和Kuppfer细胞，分别加入TxA_2类似物（STA_2）、TxA_2抑制剂（OKY-046）和PGI_2类似物（OP-2507）培养，观察肝细胞损伤程度。此外，我们使用与这些细胞的共培养系统来评估这些药物的间接作用。（结果）STA_2对广泛肝切除术后分离的肝细胞具有细胞毒性作用，损伤质膜和线粒体，而OP-2507 ...更多信息对这些细胞具有细胞保护作用，抑制这些变化。OP-2507对Kuppfer细胞产生TxA_2有抑制作用。OKY-046对肝细胞无直接作用，但对Kuppfer细胞产生TxA_2有抑制作用。共培养实验表明，OP-2507和OKY-046对肝细胞均有保护作用。我们得出的结论是，OP-2507具有直接和间接作用，而OKY-046具有间接作用。我们以前的体内实验显示门静脉血中TxB_2水平升高。我们感兴趣的是门脉器官的作用，特别是脾。分离脾巨噬细胞，测定其产生TxA_2的能力。结果表明，广泛肝切除后分离的肝细胞产生TxA_2的能力增强，OKY-046对该细胞产生TxA_2有抑制作用。OKY-046对Kuppfer细胞和脾巨噬细胞产生TxA_2均有抑制作用。目前，我们正试图用类似的细胞生物学方法阐明肠在广泛肝切除术后的作用及梗阻性黄疸时肝损伤的原因。少