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术后外周血中TxB_2和6-KF水平升高，特别是在肝功能衰竭的情况下，给予TxA_2抑制剂或PGI_2类似物可改善残肝功能和生存率。在此基础上，我们对大鼠肝切除术后肝损伤的原因进行了探讨，并利用离体细胞评价了TxA_2抑制剂和PGI_2类似物对肝脏的影响。（方法）取杂种犬肝切除84%后的肝细胞和Kuppfer细胞，分别在TxA_2类似物（STA_2）、TxA_2抑制剂（OKY-046）和PGI_2类似物（OP-2507）的作用下培养，评价肝细胞的损伤程度。此外，我们利用与这些细胞共培养系统评估了这些药物的间接作用。（结果）STA_2对大范围肝切除术后分离的肝细胞具有细胞毒作用，损伤质膜和线粒体，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对kupfer细胞产生TxA_2具有抑制作用。OKY-046对肝细胞无直接作用，但对库普弗细胞产生TxA_2有抑制作用。共培养系统实验表明，OP-2507和OKY-046对肝细胞均有细胞保护作用。我们得出OP-2507具有直接和间接效应，而OKY-046具有间接效应。我们之前的体内实验显示门静脉血中TxB_2水平升高。我们对门静脉器官，尤其是脾脏的作用很感兴趣。然后分离脾脏巨噬细胞，评价其产生TxA_2的能力。结果表明，大范围肝切除术后分离的细胞产生TxA_2增加，OKY-046对细胞产生TxA_2有抑制作用。结果表明，OKY-046不仅对库普弗细胞产生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。目前，我们正试图利用类似的细胞生物学方法，阐明广泛肝切除术后肠的作用和梗阻性黄疸肝损伤的原因。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