骨髓间充质干细胞对染矽尘大鼠肺纤维化干预作用

Intervening effect of bone marrow-derived mesenchymal stem cells for silica-induced pulmonary fibrosis in rats

目的探讨骨髓间充质干细胞(BMMSCs)对染矽尘大鼠不同时期肺纤维化的干预作用。方法无特定病原体级SD大鼠随机分为模型组、2周组、4周组和对照组,每组6只,雌雄各半。采用一次性非暴露式气管注入法,前3组大鼠予0.5 mL质量浓度为30 g/L的无菌矽尘悬液,对照组大鼠予等体积0.90%氯化钠溶液。2周组、4周组大鼠分别在染尘后第2和4周经尾静脉单次注射0.5 mL细胞密度为5×10~9/L的BMMSCs悬液,模型组和对照组大鼠予等体积0.90%氯化钠溶液。染尘后第12周对4组大鼠进行肺部计算机断层扫描(CT)检查,观察大鼠肺部组织病理改变,检测肺脏脏器系数、肺组织羟脯氨酸(HYP)及血清转化生长因子β1(TGF-β1)的水平。结果肺部CT显示:对照组大鼠肺野清透,肺纹理清晰;模型组大鼠肺部见弥漫分布、大小不一的颗粒状高密度影及条索状或网状纤维影;2周组大鼠肺部可见散在分布的细小颗粒状阴影;4周组大鼠肺部可见散在的颗粒状高密度影及网状阴影,颗粒大小及分布面积均小于模型组。模型组、2周组和4周组大鼠肺部CT值、肺脏脏器系数、肺组织HYP水平和血清TGF-β1水平均高于对照组(P<0.05)。肺部CT值、肺组织HYP水平和血清TGF-β1水平从低到高依次为对照组<2周组<4周组<模型组(P<0.05);模型组和4周组大鼠肺脏脏器系数均高于2周组(P<0.05)。结论 BMMSCs可减轻矽尘导致的肺纤维化,在纤维化早期应用效果更佳。

Objective To explore the intervening effects of bone marrow-derived mesenchymal stem cells （BMMSCs） for pulmonary fibrosis of rats exposed to silica dust at different stages.Methods Specific pathogen free SD rats were randomly divided into model group,2-week group,4-week group and control group with 6 rats in each group （half males and half females）.Rats of the first three groups were one-time endotracheally injected with 0.5 mL aseptic silica suspension at 30 g/L mass concentration.Rats of control group were injected with 0.5 mL 0.90% sodium chloride solution.Rats of 2-week group and 4-week group were injected with 0.5 mL BMMSCs suspension with cell density was 5×109/L at 2 weeks and 4 weeks respectively after silica dust exposure,while model group and control group were injected with aseptic 0.90% sodium chloride solution in the same volume.After that all rats were examined by lung computed tomography （CT） scan,pathological sections were observed,lung coefficient were measured,lung tissue hydroxyproline （HYP） content and serum transforming growth factor β1 （TGF-β1） concentration were investigated at the 12th week after silica dust exposure.Results Lung CT image showed clean lung field and clear pulmonary parenchyma in control group.Multiple and diffused high density granular shadows of different size and streak/reticular fiber shadows in model group;diffused distribution of very small granular shadows in 2-week group;granular shadows and local reticular fiber shadows in 4-week group,and either the size or the area of granular shadows was smaller than model group.The lung CT value,lung coefficient,lung tissue HYP content and serum TGF-β1 concentration of model group,2-week group and 4-week group were higher than those of control group （P〈0.05）.The lung CT value,lung tissue HYP content and serum TGF-β1 concentration of control group,2-week group,4-week group and model group were elevated in turn （P〈0.05）,while the lung coefficient of model group and 4-week group was higher than that of 2-week group respectively （P〈0.05）.Conclusion BMMSCs could delay pulmonary fibrosis caused by silica dust,and the protective effect is better at early stage than later stage of fibrosis.