目的 探讨青蒿琥酯（ART）减轻急性移植物抗宿主病（aGVHD）小鼠肠黏膜屏障损伤的机制，以及ART与地塞米松（DXM）联合治疗aGVHD小鼠的协同效应。 方法 通过骨髓造血干细胞移植建立aGVHD小鼠模型。将小鼠分为正常对照组、aGVHD组、正常小鼠ART组［30 mg/(kg·d)］、aGVHD小鼠低剂量ART组［10 mg/(kg·d)］、aGVHD小鼠中剂量ART组［30 mg/(kg·d)］、aGVHD小鼠高剂量ART组［50 mg/(kg·d)］、aGVHD小鼠DXM组［20 mg/(kg·d)］、aGVHD小鼠ART［30 mg/(kg·d)］+DXM组［20 mg/(kg·d)］、aGVHD小鼠ART［30 mg/(kg·d)］+减半DXM组［10 mg/(kg·d)］，共9组。评估小鼠生存率及临床参数；HE染色和阿利新蓝过碘酸雪夫(AB-PAS)染色观察肠黏膜组织病理改变；Real-time PCR、Western blotting和免疫组织化学技术检测肠黏膜屏障相关指标、T细胞分化转录因子、细胞因子、代谢关键酶的表达；流式细胞术检测辅助性T细胞17（Th17）和调节性T细胞（Treg）数量。 结果 ART治疗30 d后，aGVHD小鼠症状明显缓解，生存率显著提高；肠黏膜屏障结构明显恢复，通透性降低；AMP活化蛋白激酶(AMPK)/mTOR 通路活性降低，T细胞能量代谢模式以脂肪酸合成为主；Th17/Treg平衡恢复。DXM联用ART治疗aGVHD小鼠与DXM单独治疗效果相当，且小鼠生存率更高；特别是减半DXM联用ART治疗组小鼠肠黏膜屏障功能恢复最为明显。 结论 ART通过恢复Th17/Treg平衡减轻同种（allo）-T细胞对肠黏膜屏障的免疫损伤，维持了肠道黏膜屏障功能的完整性；ART与DXM联合治疗aGVHD小鼠具有协同效应，可通过减少DXM的用量降低其副作用的发生率。 

Objective To investigate the mechanism by which artesunate (ART) attenuates intestinal mucosal barrier damage in acute graft-versus-host disease (aGVHD) and the synergistic effect of ART in combination with dexamethasone (DXM) in the treatment of aGVHD mice.   Methods The aGVHD mouse model was established by bone marrow haematopoietic stem cell transplantation. The mice were divided into 9 groups, including normal mice control (Ctrl), aGVHD mice (aGVHD), normal mice receiving ART ［30 mg/(kg·d)］, aGVHD mice receiving low-dose ART［10 mg/(kg·d)］, aGVHD mice receiving medium-dose ART ［30 mg/(kg·d)］, aGVHD mice receiving high-dose ART ［50 mg/(kg·d)］, aGVHD mice receiving DXM［20 mg/(kg·d)］, aGVHD mice receiving ART［30 mg /(kg·d)］and DXM ［20 mg/(kg·d)］, and aGVHD mice receiving ART ［30 mg /(kg·d)］ and halved-DXM ［10 mg/(kg·d)］. Survival rate and clinical parameters were assessed. HE staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to observe the histopathological changes in the intestinal mucosa of the mice; Real-time PCR, Western blotting and immunohistochemistry were used to detect the structure of the intestinal mucosal barrier, the T cell differentiation related transcription factors and cytokines, and the key enzymes of energy metabolism. Flow cytometry was used to detect the T helper cell 17(Th17) and regulatory T cells(Treg).    Results After 30 days of ART treatment, aGVHD mice showed significant relief of systemic symptoms and increase in survival rate. In aGVHD mice treated with ART, the intestinal mucosal barrier structure was restored, and the intestinal mucosal permeability was reduced. The activity of AMP-activated protein kinase (AMPK)/mTOR pathway was inhibited, and the energy metabolism pattern of T cells was dominated by fatty acid synthesis. The balance of Th17/Treg was restored due to the decrease of Th17 and the increase of Treg. The effect of ART+DXM treatment on aGVHD mice was comparable to that of DXM treatment alone, and the survival rate of mice was higher. In particular, the recovery of the intestinal mucosal barrier function was most obvious in the mice treated with ART + half-dose DXM.    Conclusion ART reduces the immune injury of allo-T cells to the intestinal mucosal barrier by recovering the Th17/Treg balance, thus maintaining the integrity of the intestinal mucosal barrier function. The synergistic effect of ART and DXM combination treatment in aGVHD mice can reduce the incidence of DXM side effects by decreasing the dosage of DXM.