骨髓间充质干细胞移植清除急性肺损伤大鼠的肺泡液体

背景：肺泡液体增多是急性肺损伤的重要病理生理改变，而修复受损的肺泡-毛细血管膜屏障是减轻肺水肿的有效途径。 目的：探讨骨髓间充质干细胞移植对内毒素诱导急性肺损伤模型大鼠肺泡液体的清除作用。 方法：采用改良的Peister法分离培养大鼠骨髓充质干细胞，传至第3代制成单细胞悬液。将大鼠随机分为3组，急性肺损伤组和骨髓间充质干细胞干预组采用腹腔注射内毒素建立急性肺损伤模型。成功造模1 h后，干预组经尾静脉注射骨髓间充质干细胞悬液0.5 mL(细胞数1×106个)，对照组和损伤组同法予以等量生理盐水。各组在尾静脉注射后6，24，48 h，检测肺泡液体清除率、肺水含量程度测定，观察肺组织病理变化。 结果与结论：肺水含量程度测定湿干比肺损伤组在24 h点与其他组比明显升高(P < 0.05)；细胞移植组湿干比在各时间点与肺损伤组比明显降低(P < 0.05)。细胞移植组在各时间点肺泡液体清除率与肺损伤组比明显升高(P < 0.05)。苏木精-伊红染色光镜观察，肺损伤组6 h点表现为毛细血管充血，肺泡腔内炎性细胞浸润，24 h点加重；细胞移植组6 h点肺泡腔内炎性细胞浸润较肺损伤组轻，24 h点继续减轻，48 h点基本接近正常对照组。提示，骨髓间充质干细胞移植可能通过能修复受损的肺泡-毛细血管膜屏障从而增加急性肺损伤大鼠肺泡液体清除。

Effect of bone marrow mesenchymal stem cell transplantation on alveolar fluid clearance in acute lung injury rats

BACKGROUND: The increase of alveolar fluid is an important pathophysiological change of acute lung injury. Repairing the damaged alveolar-capillary membrane barrier is an effective way of alleviating pulmonary edema. OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on alveolar fluid clearance in endotoxin-induced acute lung injury rats. METHODS: Rat BMSCs were isolated and cultured using the modified Peister method. At the third passage, the BMSCs were made into single cell suspension. The rats were randomly divided into three groups. In the acute lung injury and cell transplantation groups, endotoxin was injected into the abdomen to establish models of acute lung injuny. One hour following model establishment, the intervention group, by caudal vein injection, was injected with BMSC suspension of 0.5 mL (cell count 1 × 106), and the control group and damage group were given the equal volume of normal saline. For each group, the rate of alveolar fluid clearance was measured, the lung water content level was assayed, and the pathological changes of lung tissue were observed after tail vein injection at 6, 24 and 48 hours respectively. RESULTS AND CONCLUSION: The lung water content level assay showed that the wet to dry ratio for lung injury group was significantly higher (P < 0.05) at 24 hours, compared with the normal control group and cell transplantation group. Compared with the lung injury group, the wet to dry ratio of the cell transplantation group was significantly lower (P < 0.05) at various time points. For the cell transplantation group, the rate of alveolar fluid clearance was significantly higher at various time points, compared with the lung injury group (P < 0.05). By hematoxylin-eosin staining microscopy, the lung injury group showed capillary congestion and alveolar infiltration of inflammatory cells at 6 hours, which aggravated at 24 hours. The cell transplantation group showed that at 6 hours the alveolar space infiltration of inflammatory cells was better, compared with the lung injury group, which continued to get better at 24 hours and become basically close to the normal control group at 48 hours. This indicated that BMSC transplantation may be able to promote the alveolar fluid clearance in acute lung injury by repairing damaged alveolar-capillary membrane barrier.