昆明山海棠提取物预防急性移植物抗宿主病的实验研究

An experimental study of Tripterygium hypoglaucum Hutch extract in the prophylaxis of acute graft-versus-host disease in mice

目的观察昆明山海棠(THH)提取物在急性移植物抗宿主病(aGVHD)中的作用及其可能的作用机制。方法建立aGVHD模型,BALB/c受鼠清髓性预处理后分别用生理盐水、环孢素A(CsA)、THH及CsA+THH混合物灌胃。观察移植后受鼠aGVHD、生存时间、CD4+/CD8+比率、CD4+CD25+T细胞比率及脾细胞Foxp3 mRNA水平。结果生理盐水组出现典型aGVHD,20天内全部死亡。其余3组aGVHD临床、病理表现及生存时间均改善,组间无差异;CD4+/CD8+比率、受鼠CD4+CD25+T细胞比率及脾Foxp3 mRNA表达较生理盐水组升高,以联用组明显。结论THH可减轻小鼠aGVHD,延长其生存时间。机制可能与增加CD4+CD25+T细胞比率,上调Foxp3 mRNA表达,调节CD4+/CD8+比率有关。THH和小剂量CsA联合有协同作用。

Objective To observe the prophylactic effect of Tripterygium hypoglaucum Hutch（THH） extract on acute graft-versus-host disease（aGVHD） in mice following hematopoietic stem cell transplantation（HSCT）.Methods 1×10^8 bone marrow cells mixed with 1×10^8 spleen cells from C57BL/6 mice were transplanted into the death irradiated BABL/c mice to establish the aGVHD model.Recipient mice were treated with 0.9% sodium chloride（group A）,ciclosporin A（group B）,THH extract（group C） and THH combined with CsA（group D）.The signs of clinical aGVHD,histological evidence of aGVHD were assessed by survival,CD4^＋ and CD8＋ T cell subsets,CD4^＋CD25^＋ subpopulation and the expression of Foxp3 in splenocytes after HSCT.Results The medium survival time for group A was 9 days and within 20 days after HSCT,all mice died,while that in groups B,C and D was over 30 days,which was significantly longer than in group A（P〈0.05）.Group A mice exhibited significant clinical symptoms and histological signs of aGVHD,whereas those of groups B,C and D showed only mild clinical and histological signs of aGVHD.The ratio of CD4^＋ T cells/CD8^＋ T cells,percentage of CD4^＋CD25^＋ T cells and the level of Foxp3 in the spleen in groups B,C and D were higher than group A,and group D showed the maximum effect.Conclusion THH can prevent aGVHD after allogeneic bone marrow transplantation in mice.The possible mechanism is involved in the upregulation of Foxp3 expression to induce CD4^＋CD25^＋ regulatory T cells and the regulation of the CD4^＋ and CD8^＋ T cells.THH combined with CsA showed synergic effect in the prevention of aGVHD.