纤维支气管镜肺减容术在绵羊肺气肿模型中的应用

Application of bronchoscopic lung volume reduction using one-way flap device in sheep model of heterogeneous emphysema

目的 评价使用纤维支气管镜单向活瓣支架肺减容术治疗肺气肿动物模型的疗效和安全性。方法 6月龄绵羊6只，全麻下经纤维支气管镜在肺段局部给予木瓜蛋白酶（75U／kg）后，机械通气15～20min形成肺气肿模型。通过CT确定靶区后，在X线造影定位并确定靶支气管后，经纤维支气管镜通过导丝和放送装置在肺气肿亚段放入1～2个单向活瓣支架，术后给予3d抗炎治疗。在术前和术后8周测量肺功能残气量；术后8周处死动物取出完整肺组织，在萎陷区、非萎陷区和对侧正常肺组织分别取材，观察大体及光镜下病理学改变。结果 应用纤维支气管镜肺减容术后，动物耐受性较好，术后无明显咳嗽、呼吸困难症状，术后1h动物即可进食、行走。病理观察无肺部炎症、肺脓肿和肉芽肿形成，2只动物支架处支气管壁少量纤维母细胞和平滑肌及支气管黏膜上皮细胞增生，4只动物未见明显异常。支架远端肺组织大体标本和光镜下均证实存在肺不张，术后肺功能残气量较术前明显降低（降低49．5％），手术过程安全、操作简单易行。结论 经纤维支气管镜单向活瓣支架肺减容术治疗肺气肿创伤小，支架对于气管壁的刺激小，可以达到外科肺减容术的效果；所做的动物模型为不均一肺气肿，与人类发病类型很相似，故对进一步行临床研究有一定的参考价值；因术后观察时间仅为8周，支架远期对气道的损伤及其疗效需要进一步研究。

Objective To evaluate the effectiveness of bronchoscopic lung volume reduction （BLVR） using one-way flap device in sheep model of heterogeneous emphysema. Methods Six 6-month sheep （weight ：20- 30 kg） were treated with localized papain instillations to generate heterogeneous emphysema, subsequently underwent BLVR using one-way flap device at subsegment. Lung functional residual capacity （FRC） was analyzed before and 8 weeks after operation. Animals were euthanized at the 8-week time point. Lungs were removed en bloc and inflated with a supersyringe to look for areas of gross collapse. Samples were collected from collapsed and noncollapsed areas,fixed in 10% buffered formalin,made paraffin section and stained with hematoxylin-eosin （HE） to observe morphologic change of bronchi. Results BLVR was well tolerated without complications, and it reduced lung volumes （change in residual volume 49.5%）. There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyperinflated lung, improved respiratory function safely and consistently. Conclusion BLVR using one-way flap device is a minimally invasive procedure and the stimulus of the devices to walls of bronchi is slight, moreover, the technique may attain effectiveness of surgery. Therefore maybe it will be a perspective treatment of chronic obstructive pulmonary diease.