间充质干细胞归巢到大鼠肺气肿组织分化为肺血管内皮细胞

Mesenchymal stem cells homing to rat lung emphysema followed by differentiation into pulmonary vascular endothelial cells

背景:间充质干细胞具有独特的归巢、免疫调节及抗炎作用,经静脉注射移植后能归巢到损害的靶器官及组织发挥其功能,修复受损组织。目的:观察间充质干细胞移植后,肺气肿大鼠的肺组织病理改变。方法:将24只雌性Wistar大鼠随机分为实验组、对照组、健康对照组,前两组应用烟熏加气管内滴入猪胰弹性蛋白酶的方法制作肺气肿模型,造模成功后,实验组尾静脉注射BrdU标记骨髓间充质干细胞,对照组注射PBS。14 d后,检测观察大鼠肺组织病理学变化,检测肺泡灌洗液中肿瘤坏死因子α水平,肺泡壁细胞凋亡指数、抗CD34及抗Brd U免疫组织化学变化。结果与结论:①与健康对照组比较,对照组肿瘤坏死因子α水平、肺泡壁细胞凋亡指数升高(P<0.01),抗Brdu及抗CD34相对面积减少(P<0.01);与对照组比较,实验组肿瘤坏死因子α水平、肺泡壁细胞凋亡指数降低(P<0.01),抗Brdu及抗CD34相对面积增加(P<0.01);②肺组织病理学检查显示,对照组及实验组均呈现肺气肿样改变,但实验组轻于对照组;③结果表明,间充质干细胞能抑制实验性肺气肿的炎症反应及细胞凋亡,改善肺气肿病理学变化且骨髓间充质干细胞可分化为肺血管内皮细胞。

BACKGROUND:Mesenchymal stem cells have unique homing,immunoregulation and anti-inflammatory properties.After intravenous injection,mesenchymal stem cells can home to the damaged target organs and tissues,and function to repair damaged tissues.OBJECTIVE:To observe the pathological changes of lung tissues in rats with emphysema after mesenchymal stemcells transplantation.METHODS:Twenty-four female Wistar rats were randomly divided into experimental group,control group and healthycontrol group.In the first two groups,the model of pulmonary emphysema was established by the method of droppingporcine pancreatic elastase.BrdU-labeled mesenchymal stem cells were injected into the tail vein of the rats in theexperimental group,and PBS was injected in the control group.After14days,the pathological changes of lung tissueswere observed.Tumor necrosis factor-αlevel,alveolar wall apoptotic index,anti-CD34and anti-BrdUimmunohistochemical changes in the bronchoalveolar lavage fluid were detected.RESULTS AND CONCLUSION:Compared with the healthy control group,the tumor necrosis factor-αlevel and apoptoticindex of alveolar wall cells increased(P<0.01),and the relative areas of anti-Brdu and anti-CD34decreased(P<0.01)in thecontrol group.Compared with the control group,the level of tumor necrosis factor-αand apoptotic index of alveolar wall cellsdecreased(P<0.01),and the relative area of anti-Brdu and anti-CD34increased(P<0.01)in the experimental group.Thehistopathological findings showed that both the control group and the experimental group showed emphysema-like changes,but these changes were milder in the experimental group than the control group.To conclude,mesenchymal stem cells caninhibit inflammatory response and apoptosis in experimental emphysema,improve the pathological changes of the lung,andmoreover,bone marrow mesenchymal stem cells can differentiate into lung vascular endothelial cells.