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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。
In this study, Tripterygium wilfordii was used to control acute graft-versus-host disease in mice. A lethal dose of C57BL/6 mice was injected with a mixture of BABC/c bone marrow and spleen lymphocytes from the donor mice and treated with triptolide, cyclosporine A, and methotrexate. Immunohistochemistry, flow cytometry, and ELISA were used to detect T lymphocytes, adhesion molecules, and cytokines in each group of mice. The results showed that all allogeneic control mice died of aGVHD within 30 days, while Tripterygium wilfordii group (19/21), cyclosporine A+ methotrexate group (13/21) and Tripterygium wilfordii + Most of the mice in the cyclosporine A group (17/21) survived for more than 30 days and showed no apparent symptoms of aGVHD. Tripterygium wilfordii, cyclosporin A, and methotrexate significantly decreased CD3+, CD4+, CD8+, CD11a+, and CD18+ cells in the skin and lung tissues (P<0.05) and spleen tissues CD3+, CD4+, CD8+, CD4+CD11a+, and CD4. +CD18+, CD8+CD11a+, CD8+CD18+ cells (P<0.05). However, there was no significant change in CD3+, CD4+, and CD8+ cells in the small intestine (P>0.05). At the same time, Tripterygium wilfordii can reduce the levels of IL-2 and TNFα in serum and the expression of IL-2 and TNFα mRNA in spleen (P<0.05), and up-regulate the levels of IL-10 in serum (P<0.05). However, the effect of IL-4 was not significant (P>0.05). Conclusion: Tripterygium wilfordii has obvious anti-aGVHD effect and retains anti-leukemia effect. The mechanism is related to regulating the secretion of proinflammatory and anti-inflammatory cytokines, the expression of adhesion molecules, and inhibiting the effect of T lymphocytes.