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

在体内实验中，我们报道了广泛肝切除后外周血中TxB_2和6-KF水平的升高，特别是在肝功能衰竭的病例中，加入TXA_2抑制剂或PGI_2类似物可改善残肝功能和提高存活率。然后，我们利用分离的细胞来阐明广泛肝切除后肝损伤的原因，并评价TXA2抑制剂和PGI2类似物对肝脏的影响。(方法)在杂种犬84%肝切除后分离肝细胞和Kuppfer细胞，加入TXA2类似物(STA2)、TXA2抑制剂(OKY-046)或PGI2类似物(OP-2507)培养，评价肝细胞损伤程度。此外，我们利用与这些细胞的共培养系统评估了这些药物的间接作用。(结果)STA2对大鼠肝切除术后分离的肝细胞具有细胞毒作用，损伤肝细胞质膜和线粒体，而OP-2507…MORE对这些细胞具有细胞保护作用，抑制这些变化。OP-2507具有抑制Kuppfer细胞产生TXA2的作用。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。我们认为OP-2507既有直接作用又有间接作用，而OKY-046有间接作用。我们先前的体内实验显示，门静脉血中TxB_2水平升高。我们对门脉器官的作用很感兴趣，特别是脾。分离脾巨噬细胞，评价其产生TXA2的能力。提示大鼠肝切除后分离的细胞产生TXA2的增加，以及OKY-046对该细胞产生TXA2的抑制作用。结论OKY-046不仅对Kuppfer细胞产生TXA_2有抑制作用，而且对脾巨噬细胞产生TXA_2也有抑制作用。现在，我们正试图用类似的细胞生物学方法来阐明广泛肝切除术后肠道的作用以及梗阻性黄疸时肝损伤的原因。较少

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