J2小分子化合物能有效抑制小鼠急性移植物抗宿主反应的实验研究

Effective immunosuppressive effect of J2 on GVHD in a mice model of allo-bone marrow transplantation

目的:采用小鼠急性移植物抗宿主疾病(aGVHD)模型,对小分子化合物(J2)体内免疫抑制活性进行初步评价。方法:以近交系C57BL/6(H-2K^b)小鼠作为供者,BALB/c(H-2K^d)小鼠作为受者,给予受者鼠8 Gy^(60)Co全身照射,4～6 h后行骨髓细胞与脾细胞移植。通过对受体鼠基因型的检测、aGVHD发生的基本特征、生存期以及器官组织的病理学分析,对J2可能的预防或治疗作用做初步评估。结果:建立的异基因骨髓移植动物模型具有aGVHD的基本特征,可用于免疫抑制化合物的体内评价。与未给药对照相比,J2口服喂药能够有效延长aGVHD小鼠的生存时间,并能减轻aGVHD所导致的皮肤、肝、小肠以及脾脏等组织病理损伤,呈一定的剂量依赖效应。结论:小分子化合物J2在体内具有一定的免疫抑制功能。

Objective： To determine the possible immunosuppressive activity of J2 in vivo by using a mouse model of allo-bone marrow transplantation （allo-BMT）. Methods： After J2 oral administration, the genotype of the peripheral blood lymphocytes, the characteristics of aGVHD, the survival time as well as the histopathological sections, involving the skin, liver, small intestine, spleen and kidney of the recipient mice were analyzed in comparison with the untreated control animals. Results：Compared with the untreated control group, J2 administration was shown to prolong the median survival time of the recipient mice in a dose-dependent fashion. The damage to the recipient mice treated with J2, including skin, liver, small intestine as well as spleen, were lessened in comparison with the untreated animals, although all these organs were not recovered to normal. Conclusion：J2 Possesses some immunosuppressive activity in vivo.