| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
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
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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
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