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

本研究采用小鼠骨髓移植模型，对移植物抗宿主病的治疗进行了研究。采用动物模型研究地塞米松棕榈酸酯（D-PAL）脂质微球（D-PAL乳剂）对慢性GVHD的影响。对BALB/c小鼠进行致死性辐照，并给予来自B10.D2小鼠的脾细胞和骨髓细胞。这些小鼠在主要组织相容性复合体（MHC，H-2 d）和次要淋巴细胞刺激位点（Mls，B）上相同。移植后数周，BALB/c受体表现出脱发、体重减轻、淋巴结和脾脏萎缩，最终死于慢性GVHD。将D-PAL乳剂给予该GVHD小鼠模型以研究该药物对GVHD的作用，并将D-PAL乳剂的作用与水溶性类固醇甲基强的松龙（m-PSL）的作用进行比较。当小鼠在移植后第2天用D-PAL乳剂处理，然后每3或4周处理一次时，94%的小鼠在20周时存活，只有12%的小鼠出现脱发。这些数据显著优于给予m-PSL的小鼠（存活率：63%）或未给予任何治疗的小鼠（存活率：37%）。尸检显示，给予D-PAL乳剂的存活受体小鼠在皮肤、淋巴结、脾和肝中没有显示出显著变化，而未处理的受体和给予m-PSL的受体显示出组织减少和破坏，在这些组织中有T细胞浸润，即使它们存活。

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.