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雷公藤氯仿提取物对小鼠慢性移植物抗宿主病的抑制作用

Inhibition of murine chronic graft-versus-host disease by the chloroform extract of Tripterygium wilfordii Hook f.

作者信息

Asano K, Yu Y, Kasahara T, Hisamitsu T

机构信息

Department of Medical Biology, School of Medicine, Showa University, Tokyo, Japan.

出版信息

Transpl Immunol. 1997 Dec;5(4):315-9. doi: 10.1016/s0966-3274(97)80015-9.

DOI:10.1016/s0966-3274(97)80015-9
PMID:9504154
Abstract

The effects of chloroform extract of Tripterygium Wilfordii Hook f (TWH extract) on chronic graft-versus-host disease (GVHD) were examined in a murine experimental model. Chronic GVHD was induced by intravenous transfer of parental DBA/2 spleen cells into unirradiated (C57BL/6 x DBA/2)F1 recipient mice. The effects of TWH extract on GVHD were assessed by measuring both the degree of splenomegaly and the total serum IgE levels 3 weeks after the cell transfer. Subcutaneous administration of TWH extract once a day for 3 weeks suppressed chronic GVHD in a dose-dependent manner. Significant suppression of splenomegaly was first noted in mice treated with 7.5 micrograms/kg of the agent. The maximum inhibition was observed when mice were treated with more than 10.0 micrograms/kg (but not 5.0 micrograms/kg) caused complete suppression of serum IgE hyperproduction. The ability of donor T cells purified from recipient spleen cells to produce interleukin 4 in response to stimulation with anti-CD3 monoclonal antibody was significantly abrogated when recipient mice were treated with 10.0 micrograms/kg of the agent. These results strongly suggest that TWH extract will be an addition to the cohort of immunosuppressive therapies used in solid organ and bone marrow transplantation.

摘要

在小鼠实验模型中检测了雷公藤多苷提取物(TWH提取物)对慢性移植物抗宿主病(GVHD)的影响。通过将亲代DBA/2脾细胞静脉注射到未受照射的(C57BL/6×DBA/2)F1受体小鼠中诱导慢性GVHD。在细胞转移3周后,通过测量脾肿大程度和血清总IgE水平来评估TWH提取物对GVHD的影响。每天皮下注射TWH提取物,持续3周,以剂量依赖方式抑制慢性GVHD。在用7.5微克/千克该药物治疗的小鼠中首次观察到脾肿大的显著抑制。当用超过10.0微克/千克(而非5.0微克/千克)治疗小鼠时观察到最大抑制,导致血清IgE过度产生完全受到抑制。当用10.0微克/千克该药物治疗受体小鼠时,从受体脾细胞中纯化的供体T细胞在抗CD3单克隆抗体刺激下产生白细胞介素4的能力显著被消除。这些结果强烈表明,TWH提取物将成为实体器官和骨髓移植中使用的免疫抑制疗法群体中的一员。

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