人胎盘间充质干细胞降低肺泡上皮屏障通透性缓解小鼠急性肺损伤  

Human Placental Mesenchymal Stem Cell Transplantation Reduce the Permeability of Alveolar Epithelial Barrier and Alleviate Acute Lung Injury in Mice

作　　者：喻文琴 吕玉珍 胥海欢 韩佩佩 马晓薇 YU Wenqin;LYU Yuzhen;XU Haihuan;HAN Peipei;MA Xiaowei(Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China;Ningxia Institute of Human Stem Cells,Yinchuan 750004,China;Intensive Care Unit,Cardiocerebral Vascular Disease Hospital of General Hospital of Ningxia Medical University,Yinchuan 750002,China)

机构地区：[1]宁夏医科大学临床医学院,银川750004 [2]宁夏人类干细胞研究所,银川750004 [3]宁夏医科大学总医院心脑血管病医院ICU,银川750002

出　　处：《宁夏医科大学学报》2023年第2期117-123,共7页Journal of Ningxia Medical University

基　　金：国家自然科学基金项目(81860350);宁夏自然科学基金项目(2020AAC02002)。

摘　　要：目的探讨人胎盘间充质干细胞(hPMSCs)对急性肺损伤(ALI)小鼠肺泡上皮屏障通透性的影响。方法将24只雄性C57BL/6J小鼠随机分成对照组、ALI组、hPMSCs组,每组8只,气管滴注脂多糖(LPS)制备ALI模型,12 h后,hPMSCs组尾静脉注射hPMSCs,对照组尾静脉注射等量DMEM,24 h后处死小鼠,收集肺组织。苏木-伊红(HE)染色观察各组小鼠肺组织病理改变并评分,检测肺组织湿干重比(W/D),计算肺泡灌洗液(BALF)与血清中伊文思蓝的比值检测肺泡上皮屏障通透性,免疫组化、Western blot检测肺组织紧密连接蛋白occludin的表达。结果hPMSCs成脂及成软骨诱导分化培养后染色均呈阳性,其表面特异性抗原CD73高表达,未检测到造血标记物CD34的表达。与对照组相比,ALI组肺组织病理损伤严重,肺损伤评分、W/D值、肺泡上皮屏障通透性均增加(P均<0.01),免疫组化和Western blot显示occludin蛋白表达降低(P<0.001)。与ALI组相比,hPMSCs组肺组织病理损伤减轻,肺损伤评分、W/D值、肺泡上皮屏障通透性均降低(P均<0.05);免疫组化和Western blot结果显示occludin蛋白表达升高(P<0.01)。结论hPMSCs可能通过降低肺泡上皮屏障通透性减轻小鼠ALI。Objective To investigate the effect of human placental mesenchymal stem cells(hPMSCs)on the permeability of alveolar epithelial barrier in mice with acute lung injury(ALI).Methods Twenty-four femal C57BL/6J mice were randomly divided into three groups:the control group,the ALI group,and the hPMSCs group,8 in each group.ALI mice model was induced by tracheal instillation of LPS.After 12 hours,the hPMSCs group was injected hPMSCs via tail vein,the control group was injected with the same volume of normal saline in the same way,and the mice were sacrificed 24 hours later,collect lung tissue.Hematoxylin-eosin(HE)staining was used to observe and score the pathological changes of lung tissue in each group.The wet/dry ratio(W/D)of lung tissue,the ratio of Evans blue in bronchoalveolar lavage fluid(BALF)to Evans blue in serum were measured to detect the permeability of alveolar epithelial barrier.Immunohistochemistry and Western blot were used to detect the expression of tight junction protein occludin in lung tissue.Results Both adipogenic and chondrogenic differentiation culture of hPMSCs showed positive staining.The surface-specific antigen CD73 was highly expressed,but the hematopoietic marker CD34 was not expressed.Compared with the control group,the pathological damage of lung tissue in the ALI group was severe,and the lung injury score,W/D value,and alveolar epithelial barrier permeability were all increased(P all<0.01).Immunohistochemistry and Western blot showed that the expression of occludin protein decreased(P<0.001).Compared with the ALI group,the pathological damage of lung tissue in the hPMSCs group was alleviated,and the lung injury score,W/D value,and alveolar epithelial barrier permeability were all decreased(P all<0.05).Immunohistochemistry and Western blot results showed that the expression of occludin protein increased(P<0.01).Conclusion hPMSCs may protect the lung injury of ALI mice by reducing the permeability of the alveolar epithelial barrier.

关 键 词：人胎盘间充质干细胞 急性肺损伤 肺泡上皮屏障 

分 类 号：R563[医药卫生—呼吸系统] R392.11[医药卫生—内科学]