ANALYSIS OF MICROCHIMERISM BY TRANSPLANT PRETREATMENT OF ALLOANTIGEN OR XENOANTIGEN IN LIVER AND SMALL BOWEL TRANSPLANTATION

肝脏和小肠移植中同种异体抗原或异种抗原移植预处理的微嵌合分析

• 批准号: 09470252
• 负责人: TASHIRO Seiki
• 金额: $ 8.26万
• 依托单位: THE UNIVERSITY OF TOKUSHIMA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09470252/
• 关键词: small bowel transplantation; liver transplantation; immuno-tolerance; heat shock protein; ischemic-reperfusion injury; anti-apoptosis action; 免疫寛客; 熱ショック蛋白質; 免疫寛容; microchimerism; ドナー脾細胞; GVHD; リンパ球混合培養試験; FK506; ドナー抗原

We had three execution plan trough the 1997-2000 year.1. In regard to microchimerism induction study, combined administration of the donor splenocytes and FK506 with the short periadministration. reduced allograft rejection and prolonged survival in the rat model of small bowel transplantation.2. In regard to studies about anti-apoptosis action of non-toxic HSP 70 inducer, geranylgeranylacetone (GGA), GGA administration induced HSP 70 on hepatocytes exposed to hydrogen peroxide (H202) or ethanol and exerted anti-apoptosis action. These results suggest that GGA may have a potential benefit for the treatment of liver injury. Next, we examined the effects of GGA on acute hepatic injury after 95% hepatectomy in rats. All of 25 rats with vehicle died within 60 hours after 95% hepatictomy, while 10 Of 25 rats with GGA survived. And GGA significantly suppressed the release of transaminases and IL-6 and completely inhibited TNF-α production. The examination is being carried out in the ischemic liver transplantation model at present.3. In this study, we examined the effect of FK506 and OKY046 (Tromboxane Synthase I nhibitor) against warm ischemia-reperfusion injury on non-heart-beating donor (NHBD) in orthotopic liver transplantation in rats. The 14 days survival rate in FK506 and OKY046 combined group was 100%, 83% in FK506 group, 83% in OKY046 group, compared to only 33% in control group. And serum AST, ALT, LDH, IL6 and TNF-α concentration after reperfusion were significantly improved in FK506 and OKY046 combined group, in FK506 group and in OKY046 group.

从1997年到2000年，我们有三个执行计划。在微嵌合体诱导研究中，供体脾细胞和FK 506联合给药，围给药期较短。减少大鼠小肠移植排斥反应，延长移植物存活时间.在关于无毒HSP 70诱导剂香叶基香叶基丙酮（GGA）的抗凋亡作用的研究中，GGA给药诱导了暴露于过氧化氢（H2 O2）或乙醇的肝细胞上的HSP 70，并发挥抗凋亡作用。这些结果表明，GGA可能对治疗肝损伤有潜在的益处。接下来，我们研究了GGA对大鼠95%肝切除术后急性肝损伤的影响。所有25只溶剂组大鼠在95%肝切除后60小时内死亡，而25只GGA组大鼠中有10只存活。GGA能显著抑制转氨酶和IL-6的释放，完全抑制TNF-α的产生。目前正在缺血性肝移植模型上进行研究.本研究观察了FK 506和OKY 046（Tromboxane Synthase Inhibitor）对大鼠原位肝移植中无心跳供体（NHBD）热缺血再灌注损伤的保护作用。FK 506和OKY 046联合治疗组14天生存率为100%，FK 506组为83%，OKY 046组为83%，而对照组仅为33%。FK 506与OKY 046联合组、FK 506组和OKY 046组再灌注后血清AST、ALT、LDH、IL 6和TNF-α浓度均明显降低。

项目成果

T.Miyauchi,M.Ishikawa,S.Tashiro et al.: "Effect of Donor-Specific Splenocytes via Portal vein and FK 506 in Rat Small Bowel Transplantation"Transplantation. 65. 27-32 (1998)

T.Miyauchi、M.Ishikawa、S.Tashiro 等人：“通过门静脉和 FK 506 的供体特异性脾细胞在大鼠小肠移植中的作用”移植。

Miyauchi T,Ishikawa M,Tashiro,S, et al: "Acetaminophen absorption test as a maker of small bowel transplant rejection"Transplantation. 63. 1190-1197 (1997)

Miyauchi T，Ishikawa M，Tashiro，S，等人：“对乙酰氨基酚吸收试验作为小肠移植排斥反应的标志”移植。

Miyauchi T, Ishikawa M, Tashiro S, Hisaeda H, Himeno K: "Experimental study of combined treatment with tacrolimus and donor-specific splenocytes via the portal vein in small bowel transplantation."J Med Invest. (In press).

Miyauchi T、Ishikawa M、Tashiro S、Hisaeda H、Himeno K：“在小肠移植中通过门静脉使用他克莫司和供者特异性脾细胞联合治疗的实验研究。”J Med Invest。

Miyauchi T, Ishikawa M, Tashiro S: "Evaluation of the acetaminophen absorption test for the early detection of orthotopic small bowel transplant rejection."Surg Today. (In press).

Miyauchi T、Ishikawa M、Tashiro S：“对乙酰氨基酚吸收试验的评估，用于早期发现原位小肠移植排斥反应。”今日外科。

Miyauchi T, Ishikawa M, Tashiro S, Hisaeda H, Nagasawa H, Himeno K: "Acetaminophen absorption test as a maker of small bowel transplant rejection."Transplantation. 63. 1179-1190 (1997)

Miyauchi T、Ishikawa M、Tashiro S、Hisaeda H、Nagasawa H、Himeno K：“对乙酰氨基酚吸收试验作为小肠移植排斥反应的标志。”移植。