抗PD-L1治疗在大鼠淋巴管畸形模型中的作用

Role of Anti-PD-L1 Therapy in Lymphatic Malformations Rat Models

目的:通过大鼠淋巴管畸形(lymphatic malformations,LM)动物模型,探讨抗PD-L1(programmed death ligand 1)治疗在淋巴管畸形中的作用。方法:选择20只雌性成年Wistar大鼠,体重(250±30)g,在颈部皮下注射弗氏不全佐剂(Freund's incomplete adjuvant,FIA)构建大鼠LM动物模型。然后分成4组:PBS组、抗PD-L1组、LPS组、LPS+抗PD-L1组。记录大鼠体重及病变变化,收获病变组织及重要内脏器官进行检测。并通过免疫组织化学法在人LM组织中检测PD-L1表达情况。结果:PD-L1在大鼠LM模型中有表达,在LPS作用下表达进一步升高;抗PD-L1治疗通过抑制淋巴管内皮细胞增殖和成管不仅对非炎症状态LM有治疗效果,对炎症状态下LM也有显著疗效。与正常皮肤对比,PD-L1在人LM病变中也有表达。结论:PD-L1可能与LM的病理过程密切相关,抗PD-L1治疗为LM的治疗提供新的思路。

Objective:To observe the effect of Anti-PD-L1 therapy in established LMs rat models.Methods:LMs rat models were established by injection of Freund's incomplete adjuvant(FIA)in subcutaneous to the neck in twenty female Wistar rats[(250±30)g].Rats with lesions were randomly divided into four groups with different treatment as follows:PBS only,PBS and Anti-PD-L1,PBS and LPS or PBS combination with LPS and Anti-PD-L1.The sizes of LMs lesions and body weight of rats were measured for every week.After eight weeks,all rats were euthanized and the cystic lesions and vital visceral organs were harvested for further investigation.Expression level of PD-L1 in normal skins and human LMs was detected by immunohistochemistry.Results:PD-L1 was strongly elevated in the LM lesions of rats and further increased in the presence of LPS.Anti-PD-L1 therapy showed satisfactory therapeutic effect on both non-inflammatory and inflammatory LMs by decreasing the proliferation and tubular formation of lymphatic endothelial cells.In addition,compared with normal skins,PD-L1 was also upregulated in human LM lesions.Conclusion:PD-L1 might contribute to the pathological process of lymphatic malformations.Targeting the PD-L1 might be a promising therapeutic strategy for LMs.