肠三叶因子通过自噬在急性移植物抗宿主病中发挥保护作用

Intestinal trefoil factor plays a protective role in acute graft versus host disease through aotophagy

目的:观察肠三叶因子(ITF)在急性移植物抗宿主疾病(aGVHD)中的保护作用及其机制。方法:建立C57BL/6(H-2b)小鼠至BALB/C(H-2d)小鼠的异基因骨髓移植(allo-BMT)模型,诱导aGVHD,根据处理方式不同,分成4组。空白对照组未接受任何处理;BM组仅接受骨髓细胞移植;aGVHD组同时接受骨髓细胞和脾脏细胞移植;ITF组预防性使用ITF治疗,其余处理同aGVHD组。观察比较各组小鼠aGVHD临床评分、生存时间、移植后外周血白细胞情况与自噬蛋白LC3在小肠黏膜上皮细胞内的表达。结果:成功建立并诱导aGVHD模型。与ITF组相比,aGVHD组小鼠提早出现典型的aGVHD临床症状,生存期显著缩短,移植后外周血白细胞最低值更低,上升缓慢,aGVHD临床评分增加(均P<0.05)。小肠组织免疫组织化学染色结果显示,相较于BM组和ITF组,aGVHD组LC3表达水平明显增加(P<0.05)。结论:ITF对aGVHD有保护作用,可能与ITF通过降低自噬水平改善aGVHD症状有关。

Objective： To observe the protection of ITF in acute graft versus host disease （aGVHD） mod-els, and to investigate the role of autophagy in the protective effect of ITF in aGVHD. Methods： aGVHD model was established from donor mice C57BL/6 （H-2b） to host mice BALB/C （H-2d）. According to different treat-ment, mice were divided into 4 groups. No any treatment in control group, BM group only reveiced bone mar-row transplantation, while aGVHD group received a combination of bone marrow and spleen cells, ITF group accepted prophylaxis ITF treatment on basis of aGVHD group treatment. The aGVHD level was evaluated by clinical scores, survival time, peripheral leukocyte counts and expression of LC3 by immunohistochemical stain-ing. Results： The model of aGVHD was successfully established. Compared with ITF group, aGVHD group performanced earlier aGVHD symptoms, shorter survial time, lower peripheral WBC counts and higher aGVHD clinical scores （P〈0.05）. Immunohistochemical staining （IHC） showed that aGVHD group had higher expression of LC3 compared with BM group and ITF group （P〈0.05）. Conclusion： ITF play a protective role in aGVHD, which is associated with decrease of autophagy.