STUDY OF THERAPY OF GRAFT VERSUS HOST DISEASE AFTER BONE MARROW TRANSPLANTATION USING MICE MODEL

小鼠骨髓移植后移植物抗宿主病的治疗研究

基本信息

批准号：
09670892
负责人：
AIHARA Michiko
金额：
$ 1.86万
依托单位：
YOKOHAMA CITY UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670892/
关键词：
GVHD ANIMAL MODEL THERAPY

项目摘要

We studied therapy of graft versus host disease after bone marrow transplantation using mice model. The effect of Dexamethasone palmitate (D-PAL) incorporated into lipid microspheres (D-PAL emulsion) on chronic GVHD was studied with animal model. BALB/c mice were lethally irradiated and administered spleen cells and bone marrow cells from B10.D2 mice . These mice are identical at the major histocompatibility complex (MHC, H-2 d) and at the minor lymphocyte stimulating locus (Mls, b). Weeks after transplantation, the BALB/c recipients exhibit hair loss, weight loss and atrophy of the lymph nodes and spleen and finally died due to chronic GVHD. D-PAL emulsion was administered to this GVHD mice model to investigate the effect of that drug on GVHD and to compare the effects of D-PAL emulsion with those of the water-soluble steroid, methylprednisolone (m-PSL). When mice were treated with D-PAL emulsion at day 2 after transplantation and afterward once every 3 or 4 weeks, 94% of them were survived at week 20 and only 12% of them showed hair loss. These data were significantly better than mice administered m-PSL( survival rate: 63%) or without any treatments (survival rate: 37%). Autopsy revealed that the survived recipient mice administered D-PAL emulsion showed no significant changes in skin, lymph nodes, spleen and liver, while no-treated recipients and recipients administered m-PSL showed tissue reduction and destruction with T cell infiltration in those tissues even though they survived.

我们使用小鼠模型研究了骨髓移植后移植物与宿主疾病的治疗。用动物模型研究了将棕榈酸棕榈酸酯（D-PAL）掺入脂质微球（D-PAL）对慢性GVHD的影响。 BALB/C小鼠是致命的辐照，并给予B10.D2小鼠的脾细胞和骨髓细胞。这些小鼠在主要的组织相容性复合物（MHC，H-2 D）和小淋巴细胞刺激基因座（MLS，B）处相同。移植后几周，BALB/C受体表现出淋巴结和脾脏的脱发，体重减轻和萎缩，最终因慢性GVHD而死亡。将D-PAL乳液施用到该GVHD小鼠模型中，以研究该药物对GVHD的影响，并将D-PAL乳液与水溶性类固醇，甲基泼尼松酮（M-PSL）的作用进行比较。移植后第2天用D-PAL乳液治疗小鼠，然后每3或4周一次，其中94％的人在第20周存活，只有12％的人显示出脱发。这些数据明显优于给予M-PSL的小鼠（存活率：63％）或没有任何治疗（生存率：37％）。尸检表明，生存的受体小鼠给药D-PAL乳液没有显示皮肤，淋巴结，脾脏和肝脏的显着变化，而未经治疗的受体和受体M-PSL也会显示出这些组织中T细胞浸润的组织减少，即使它们存活。