| Co-Investigator(Kenkyū-buntansha) |
高橋 直人 東京慈恵会医科大学, 医学部, 助手 (20297401)
横田 徳靖 東京慈恵会医科大学, 医学部, 助手 (80256461)
YANAGISAWA Satoru The Jikei University School of Medicine, Surgery, Associate Professor, 医学部, 講師 (80200533)
INAGAKI Yoshinori The Jikei University School of Medicine, Surgery, Associate Professor, 医学部, 助教授 (40138714)
吉田 清哉 東京慈恵会医科大学, 医学部・外科, 助手
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Purpose ; Although immunosuppressive treatment for organ transplantation has been improved greatly, rejection remains a major problem of successful small bowel transplantation (SBT). Increasing dose of immunosuppressive agents cause opportunistic infection clinically. Adding new immunosuppressive strategies are requeted. We investigated the effect of RS61443, Mycophenolate mofetil on rejection after allogeneic SBT in rats. Materials and Methods ; Inbred male ACT (RT1^a) and LEW (RT1^l) rats were used as donors and recipients, respectively. Orthotopi SBT with portcaval drainage was performed. Immunosuppressive drugs, FK506 and/or RS61443 were given to LE recipients for 2 weeks after SBT.0.1 or 0.4 mg/kg/day (low dose) of FK506 (a gift of the Fujisawa Pharmaceutical Co., Osaka, Japan) was injected intramuscularly. 20 or 40 mg/kg/day of RS61443 (donated by Syntex Inc., Palo Alto, California, USA) was ingested trans-orally using a gastric tube. LEW recipients of ACT small bowel allografts were divided into 7 groups. Group 1 ; untreated controls, Group 2 ; 0.1 mg low dose FK506, Group 3 ; 0.4 mg low *seFK5O6, Group 4 ; 20 mg RS61443, Group 5 ; 40 mg RS61443, Group 6 ; 0.1 mg FK506 + 20 mg RS61443, Group 7 ; 0.1 mg FK506 + 40 mg RS61443 (n=7 in each group). Results : Mean animal survival in Group 7 was significantly prolonged (100.0 days), when compared with 7.6 days in Group 1 or 44.7 days in Group 2 (p<0.0l, Logrank test). On the other hands, marked prolongation of animal survival was not led by the treatment with 20 (Group 4) or 40 (Group 5) mg RS61443 alone. Conclusion : These results indicate that the combination therapy of low dose FK506 and RS61443 has an important role to suppress rejection allogeneic SBT.Further studies for the mechanisms of the interaction between these drugs will be required. To elucidate the interaction, synthesis of polyamine, IL-2 and inosine monophosphate dehydrogenase will be measured.
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