【摘要】 目的通过观察骨髓间充质干细胞(bone marrow mesenchymal stem cell,BMSCs)对慢性阻塞性肺疾病(chronicobstructive pulmonary disease,COPD)模型大鼠中炎症因子、血气分析和肺组织病理学变化的影响,探讨BMSCs对COPD的治疗作用及COPD的发病机制。方法 30只健康雄性SD大鼠分成正常组、模型组和治疗组各10只。治疗组和模型组大鼠通过猪胰蛋白酶诱导建立COPD模型,正常组不处理。三组以普通饲料喂养76天后治疗组大鼠尾静脉注射BMSCs进行生物治疗,模型组及正常组给予等量生理盐水处理,继续饲养14天后处死大鼠。观察血气分析、肺组织病理学变化以及肺泡灌洗液(BALF)细胞计数与分类、IL-1β、TNF-α及IL-10水平。结果①各组大鼠动脉血气分析比较,差异无统计学意义(P>0.05)。②模型组BALF中白细胞总数、巨噬细胞数及中性粒细胞数均显著高于正常组(P<0.05),治疗组BALF中白细胞总数、巨噬细胞数及中性粒细胞数均显著低于模型组(P<0.05)。③治疗组IL-1β、TNF-α水平较正常组显著升高(P<0.05),但低于模型组(P<0.05);IL-10水平较正常组显著降低(P<0.05),但高于模型组(P<0.05);④治疗组、模型组肺组织均可见到肺气肿样改变,但治疗组较模型组肺气肿样改变减轻,平均内衬间隔(MLI)、单位面积平均肺泡数(MAN)、平均肺泡面积(MAA)差异均有统计学意义(P<0.05)。结论 BMSCs能改善COPD的病理改变;炎症反应导致的肺实质破坏和肺毛细血管减少可能是COPD主要的发病机制。更多还原

【Abstract】 To observe the effect of transplantation of bone marrow mesenchymal stem cells(BMSCs) on pathological changes of inflammatory mediators,arterial blood gas and pulmonary tissue in rat model of pulmonary emphysema,and investigate the therapeutic effects of the transplantation of BMSCs on pulmonary emphysema,and the pathogenesis of pulmonary emphysema. Thirty male SD rats were randomly divided into 3 groups:normal control group,model group and cell transplantation group.Rat model of chronic obstructive pulmonary disease(COPD) was induced by using porcine trypsin.After 76 days,in the cell transplantation group,1 mL cell suspension containing 3×106BMSCs was infused into the rat caudal vein.All rats were sacrificed at day 14 post-treatment.During the experiments,blood gas analysis was performed.After the scarification,the lung tissues were fixed and morphologic changes were examined.At the same time,bronchoalveolar lavage fluid(BALF) was collected for cell counting and classification.The expression levels of IL-1β,TNF-α and IL-10 in serum and BALF were determined by ELISAs. ①There were no significant differences in PH value,PO2,PCO2 and SaO2 among the three groups.② The total white cells and neutrophil percentage in the BALF of cell transplantation group ware significantly lower than that of the model group(P < 0.05),but higher than that of the normal control group(P < 0.05).③The levels of IL-1β and TNF-α in BALF of the cell transplantation group were higher than that of the normal control group,but lower than that in the model group.The IL-10 level of the cell transplantation group was lower than that in normal control group(P < 0.05),but higher than that of the model group(P < 0.05).④Emphysematous changes of lung tissues were observed in both the cell transplantation group and model group,but there was an obvious improvement in the cell transplantation group compared to the model group.There was statistical significance in the mean alveolar number per unit area(MAN),mean alveolar area(MAA) and mean linear interval(MLI) between the two groups. BMSCs can reverse the pathological changes of pulmonary emphysema.The destruction of lung parenchyma and the decrease of the number of pulmonary capillary induced by inflammation may be the main pathogeneses of pulmonary emphysema.更多还原