雷公藤多甙对急性移植物抗宿主病小鼠的作用

本研究应用雷公藤多甙防治小鼠急性移植物抗宿主病。对受致死量照射的C57BL／6受鼠，注入供鼠BABC／c骨髓与脾淋巴细胞的混合液，并给予雷公藤多甙、环孢素A、甲氨蝶呤处理。用免疫组织化学法、流式细胞术和ELISA法检测各组小鼠T淋巴细胞、黏附分子、细胞因子。结果表明：所有异基因对照组小鼠，在30天内死于aGVHD，而雷公藤多甙组（19／21）、环孢素A＋甲氨蝶呤组（13／21）和雷公藤多甙＋环孢素A组（17／21）的大部分小鼠存活时间超过了30天，并没有明显的aGVHD症状表现。雷公藤多甙、环孢素A、甲氨蝶呤可明显降低皮肤、肺组织CD3^＋、CD4^＋、CD8^＋、CD11a^＋、CD18^＋细胞（P〈0．05）和脾组织CD3^＋,CD4^＋，CD8^＋，CD4^＋CD11a^＋，CD4^＋CD18^＋。CD8^＋CD11a^＋，CD8^＋CD18^＋细胞（P〈0．05）。而小肠组织CD3^＋、CD4^＋、CD8^＋细胞变化不明显（P〉0．05）。同时，雷公藤多甙可降低受鼠血清中IL-2、TNFα浓度和脾组织IL-2、TNFα的mRNA的表达（P〈0．05）；上调血清中IL-10的水平（P〈0．05）。但对IL-4的作用不显著（P〉0．05）。结论：雷公藤多甙具有明显抗aGVHD作用并同时保留抗白血病效应，其作用机制与调节促炎／抑炎细胞因子的分泌和黏附分子的表达，以及抑制T淋巴细胞作用有关。

Effect of Glucosidorum Tripterygii Tororum on Acute Graft-Versus-Host Disease in Mice

To prevent acute graft-versus-host disease (aGVHD), glucosidorum tripterygii tororum (GTT) was used in the murine model. The lethally irradiated C57BL/6 recipients were injected with bone marrow and lymphocyte grafts from BALB/c donors and were treated intraperitoneally with GTT, cyclosporine A (CsA), or methotrexate (MTX). T lymphocytes, adhesion molecules and cytokines were detected by immunohistochemical method, flow cytometry, ELISA and RT-PCR, respectively. The results showed that all the control recipient mice (21/21) died of aGVHD within 30 days, but many recipient mice treated with GTT (19/21), CsA + MTX (13/21) and GTT + CsA (17/21) survived beyond 30 days without obvious signs of aGVHD. The numbers of CD3(+), CD4(+), CD8(+), CD11a(+), CD18(+) lymphocytes in skin and lung decreased markedly by GTT, GTT + CsA and CsA + MTX treatments. The numbers of CD3(+), CD4(+), CD8(+), CD4(+)CD11a(+), CD4(+)CD18(+), CD8(+)CD11a(+), CD8(+)CD18(+) lymphocytes in spleen decreased markedly by GTT, GTT + CsA and CsA + MTX treatments. and the changes of CD3(+), CD4(+), CD8(+) cells in small intestine were not remarkable (P > 0.05) by above mentioned GTT, GTT + CsA and CsA + MTX treatments. The serum concentrations and mRNA expressions of IL-2 and TNFalpha in spleens decreased significantly (P < 0.05); the concentration of IL-10 increased significantly (P < 0.05), the change of IL-4 was not remarkable (P > 0.05) by GTT treatment. It is concluded that the GTT may retain the graft-versus-leukemia (GVL) effect of transplant without aGVHD. The role of GTT in prevention of murine aGVHD is mediated by reduction of T lymphocytes and their subgroups, expression of adhesion molecule, and regulation of cytokine secretion.