苦参碱联合环孢素A减轻小鼠急性移植物抗宿主病

Matrine combined with cyclosporin A alleviates acute graft-versus-host-disease after allogeneic bone marrow transplantation in a murine model

背景:苦参碱具有降低白细胞介素2浓度的作用,作为化疗辅助用药已用于临床。目的:探讨苦参碱联合环孢素A对小鼠异基因骨髓移植后急性移植物抗宿主病发生发展的影响,及苦参碱可能的作用机制。方法:C57BL/6小鼠作为供鼠,BABL/C小鼠为受鼠,建立小鼠同种异基因骨髓移植模型。BALB/C受鼠随机分为7组:空白对照组、单纯照射组、骨髓移植组及足量环孢素A、半量环孢素A、足量苦参碱组、足量苦参碱联合半量环孢素A组。结果与结论:足量苦参碱联合半量环孢素A组小鼠生存时间明显长于其他组。进行骨髓移植的小鼠均出现不同程度病理改变,越早程度越重。移植后7d,与骨髓移植组比较,其他移植组小鼠血清γ-干扰素质量浓度下降,白细胞介素4质量浓度差异无显著性意义。提示,苦参碱能够减轻小鼠异基因骨髓移植后致死性急性移植物抗宿主病的发生,生存时间延长。苦参碱与环孢素A作用相似,二者联用,有协同作用。

BACKGROUND： Matrine can decrease the concentration of interleukin （IL-2） and has been used as a chemotherapy auxiliary medicine in the clinic. OBJECTIVE： To investigate the effects of matrine and cyclosporin A （CsA） on acute graft-versus-host-disease （aGVHD） after allogenetic bone marrow transplantation and the possible mechanism of matrine. METHODS： The donors were male C57BL/6 mice, and the recipients were male BABL/C mice. The model of aGVHD in murine was established by allo-BMT with donor derived T cells. The aGVHD models were randomly divided into seven groups： control, radiation, transplantation, fully quantity CsA, half quantity CsA, full quantity matrine, full quantity matrine and half quantity CsA. RESULTS AND CONCLUSIONS： The mouse survival time in the full quantity matrine and half quantity CsA group was longer than the other groups. Different degrees of pathological changes in aGVHD appeared in each group, and earlier aGVHD occurrence led to more severe pathological change. At 7 days after transplantation, compared with transplantation group, serum level of γ-interferon was decreased in other groups, but there was no significant difference in IL-4 level between transplantation and other groups. These findings suggest that matrine can prevent lethal aGNHD and prolong mouse survival time after allogenetic bone marrow transplantation. Matrine exhibits similar effects to CsA, and their combination show better effects than alone.