中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (2): 227-232.doi: 10.3969/j.issn.1673-8225.2010.02.009

• 血管组织构建 vascular tissue construction • 上一篇    下一篇

生长因子及骨髓间充质干细胞与肺再血管化修复烟熏大鼠肺气肿模型

李宝平，邢万红，路鹏雁，张  雷，马  捷   

  1. 山西医科大学第二医院心胸外科，山西省太原市 030001
  • 出版日期:2010-01-08 发布日期:2010-01-08
  • 作者简介:李宝平★，男，1964年生，山西省太原市人，汉族，1989年山西医科大学毕业，硕士，教授，主要从事肺减容和肿瘤综合治疗方面的研究。 libaopingmd@163.com

Influence of growth factors and bone marrow mesenchymal stem cells on lung revascularization and restoration of smoking-induced emophysematous model in rats

Li Bao-ping, Xing Wan-hong, Lu Peng-yan, Zhang Lei, Ma Jie   

  1. Department of Cardiothoracic Surgery, The Second Hospital of Shanxi Medical University, Taiyuan   030001, Shanxi Province, China
  • Online:2010-01-08 Published:2010-01-08
  • About author:Li Bao-ping★, Master, Professor, Department of Cardiothoracic Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China libaopingmd@163.com

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511

被引次数

7

摘要：

背景：作者以往研究初步证明在单纯使用胰蛋白酶制作的大鼠肺气肿模型上骨髓间充质干细胞可以“归巢”到病损肺组织，并参与肺血管形成促进肺组织修复。碱性成纤维生长因子、血管内皮生长因子同样具有强大的促进血管新生的作用。
目的：观察碱性成纤维生长因子、血管内皮生长因子、骨髓间充质干细胞对肺气肿模型大鼠肺毛细血管再生和肺气肿病理修复的影响。
方法：除正常对照组外，其余5组大鼠均采用烟熏加气管内一次性滴注猪胰弹性蛋白酶法建立肺气肿模型。成功造模后，碱性成纤维细胞生长因子组气管内注入400 U碱性成纤维细胞生长因子，血管内皮生长因子组气管内注入2 μg血管内皮生长因子，1次/周，共3次；单纯细胞移植组于尾静脉注入4×109 L-1骨髓间充质干细胞悬液1 mL；血管内皮生长因子+细胞移植组气管内注入血管内皮生长因子的同时，尾静脉注入骨髓间充质干细胞；模型对照组、正常对照组给予相同体积的生理盐水。干预4周后行动脉血气分析，观察肺组织病理改变及形态学指标变化，免疫组化法检测肺组织CD34+的表达。
结果与结论：与模型对照组比较，血管内皮生长因子组PaO2值明显升高(P < 0.05)，余指标无明显变化(P > 0.05)；其余组各项指标均无明显变化(P > 0.05)。大体及光镜观察可见，正常对照组肺表面光滑平整，呈淡粉红色，弹性好，切面可见肺泡大小均匀一致；模型对照组出现慢性阻塞性肺气肿病理改变；余4组均较模型对照组病变程度有所好转。与模型对照组比较，碱性成纤维细胞生长因子组、血管内皮生长因子组、单纯细胞移植组、血管内皮生长因子+细胞移植组平均肺泡数、CD34+相对阳性面积均明显增加(P < 0.05)，平均肺泡面积、平均内衬间隔则明显减少(P < 0.05)，此4组之间各指标比较均无明显差异(P > 0.05)。提示碱性成纤维细胞生长因子、血管内皮生长因子、骨髓间充质干细胞均能在一定程度上修复烟熏加气管内滴入弹性蛋白酶构建的大鼠肺气肿模型的病变，可能的作用机制是增加肺的毛细血管数、扩张肺血管，增加肺血流量，改善通气/血流，肺组织通过自身的代偿缩小了肺泡面积，减小肺容积。

关键词: 肺再血管化, 肺气肿, 碱性成纤维细胞生长因子, 血管内皮生长因子, 骨髓间充质干细胞, 心肺组织工程

Abstract:

BACKGROUND: Preliminary study has proved that the bone marrow-derived mesenchymal stem cells (MSCs) in a rat emphysema model produced by use of trypsin alone can "homing" to the lesioned lung tissues, and participate in the formation of pulmonary arteries to promote lung tissue repair. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) play equally a powerful role in promoting angiogenesis.
OBJECTIVE: To observe the influence of bFGF, VEGF and MSCs in regeneration of pulmonary capillary and pathological repair of pulmonary emphysema rats.
METHODS: Except normal control group, the remaining 5 groups of rats were exposed to tobacco smoke and received a single intratracheally instillation of porcine pancreatic elastase to induce emphysema models. Following successful modeling, rats of bFGF group were intratracheally injected with 400 U bFGF and rats of VEGF group with 2 μg VEGF, once a week for three times. MSCs group was injected 1 mL suspension of 4×109/L MSCs into tail vein. MSCs+VEGF group was injected MSCs into tail vein and intratracheally injected VEGF (2 ug, three times) at the same time. Model control and normal control groups were intratracheally injected with equal volume of sodium chloride. Four weeks after treatment, arterial blood gas analysis was performed to observe pathological and morphological changes of lung tissues. CD34+ expression in lung tissues was determined using immunohistochemistry method.
RESULTS AND CONCLUSION: Compared with model control group, PaO2 values dramatically increased in VEGF group (P < 0.05), while other indices remained unchanged (P > 0.05); there were no obvious changes in each index in other groups (P > 0.05). Gross and microscopic observations showed that, lung was smooth, pale pink, and elastic in normal control group, with uniform size of pulmonary alveoli on cross-section; pathological changes of chronic obstructive pulmonary emphysema existed in model control group, but improved in other 4 groups. Compared with model control group, mean pulmonary alveoli number and CD34+ relative positive area dramatically increased in bFGF, VEGF, MSCs, MSCs+VEGF groups (P < 0.05), mean linear intercept and mean alveoli area were significantly reduced (P < 0.05). No significant difference was observed in each index among these 4 groups (P > 0.05). bFGF, VEGF and MSCs could improved the pathology of pulmonary emphysema models produced by tobacco smoking and intratracheally instillation of porcine pancreatic elastase. The possible mechanism of recovering the pulmonary emphysema is the proliferation of pulmonary capillary and enlargement of pulmonary artery, improved blood flow in the lung, improved ventilation/perfusion shunt, reduced pulmonary alveolus size and volume of the lung through self-compensation.

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