内皮祖细胞移植对输血相关急性肺损伤小鼠模型保护作用的研究

摘要

目的：建立输注人类血浆小鼠输血相关急性肺损伤（TRALI）模型，观察内皮祖细胞（EPC）移植对小鼠肺部炎性免疫反应及组织病理特点的影响。方法 BALB／C 雄性小鼠36只，随机分为 TRALI 组（n＝12）：腹腔注射脂多糖（LPS），每代谢体质量用量为2 mg ，2 h 后经过静脉输注人血浆，注射量为每只1 mL ；EPC 组（n＝12）：同 TRALI 组的方法造模后，经尾静脉注入EPC（3×106个）；正常对照组（n＝10）：采用假手术处理。光镜分析各组小鼠肺组织病理及湿干比变化。采用酶联免疫吸附试验（ELISA）测定各组小鼠支气管肺泡灌洗液（BALF）中白细胞介素‐10（IL‐10）、白细胞介素‐1β（IL‐1β）、肿瘤坏死因子‐α（TNF‐α）的含量。结果 TRALI 模型组小鼠肺组织出现肺泡间隔增厚、肺泡内纤维蛋白浸润、肺泡内出血、支气管壁增厚等病理变化，肺组织湿干比增高，EPC 组以上病理变化较 TRALI 组不明显，肺组织湿干比也低于 TRALI 组，高于正常对照组（P＜0．05）。 TRALI组实验动物的 BALF 中 IL‐10、IL‐1β、TNF‐α含量均显著高于正常对照组和 EPC 组（均 P ＜0．05），EPC 组 BALF 中 IL‐10、IL‐1β、TNF‐α含量高于正常对照组（P＜0．05）。结论 EPC 移植对 TRALI 小鼠模型具有保护作用，减轻肺部炎性免疫反应及组织病理学损伤的程度。该试验为临床治疗 TRALI 提供新的视角和思路。%Objective To observe the effect of the transplantation of endothelial progenitor cells (EPCs) on the lung inflammato‐ry response and histopathology change in mice with the transfusion‐related acute lung injury (TRALI) .Methods Thirty‐six male BALB/C mice were divided into three groups randomly :normal control group(n = 12) ,TRALI model group(n = 12) ,and EPCs transplantation group(n= 12) .The TRALI model was established through human plasma injection .The LPS was intraperitoneal in‐jected in the mice of the TRALI model group ,while the normal saline was injected in the normal control group .After 2 hours ,the EPCs(3 × 106 ) were respectively injected via the tail vein in the EPCs transplantation group ,when the PBS was given in the other groups by the same way .The pathological change in lung tissue was measured by the HE staining .The ratio of wet to dry weight (W/D) was measured .The IL‐10 ,IL‐1β and TNF‐α level in the bronchial alveolar lavage fluid (BALF) was analyzed by the ELISA . Results Compared with normal control group ,the alveolar wall tissue and the bronchial wall were thickened ,the fibrin was infiltra‐ted ,the alveolar was blooding .The W/D in the TRALI model group was significantly higher than the normal control group (P <0 .05) .The above pathological changes in EPCs group were not obvious ,and the W /D in the EPCs group was lower than the TRA‐LI group ,but higher than the normal control group .The levels of IL‐10 ,IL‐1β ,and TNF‐α in the bronchial alveolar lavage fluid in the TRALI model group were significantly higher than the normal control and the EPCs group ,while these biochemical indexes in the EPCs group were also higher than the normal control group (P < 0 .05) .Conclusion EPC transplantation have a protecting function on the mice with the transfusion‐related acute lung injury ,can relieve the inflammation response in the lung tissue and the pathological change .The study has provided a new view for the clinic treatment of the TRALI .