125I碳纳米管覆膜金属支架生物安全性的实验研究

目的 探讨¹²⁵I碳纳米管覆膜金属支架对兔正常食管的生物安全性。方法 新西兰大白兔18只,用随机数字表进行完全随机化法分3组,每组6只。分别采用普通覆膜支架和放射性支架(¹²⁵I碳纳米管覆膜支架),放射性支架组又分为低活度组(3.7~5.6 MBq)和高活度组(11.1~13.0 MBq)。在数字血管造影机(DSA)透视引导下,将支架植入兔的食管中段,术后0.5 h、7、14和30 d行食管造影,并三维DSA重建,了解支架位置及通畅情况。结束实验后行放置支架段食管的病理学检查。结果 除普通覆膜支架组和低活度放射性支架组各有1只实验兔因术后肺部感染分别于手术后1和3 d死亡外,其他均顺利完成实验。实验结束后,高活度放射性支架组出现3例(3/6)食管穿孔,其中1例形成食管纵隔瘘;普通覆膜支架组和低活度放射性支架组无穿孔。病理学检查发现,放射性支架组食管黏膜坏死脱落,溃疡形成,黏膜下层、平滑肌层肌纤维肿胀、断裂,炎细胞浸润,高活度组在坏死的程度和深度上都明显高于低活度组。而普通覆膜支架组黏膜下有少量炎细胞浸润,肌层纤维部分断裂,未发现黏膜坏死脱落,溃疡形成。结论 兔食管植入放射性活度为3.7~5.6 MBq的¹²⁵I碳纳米管覆膜金属支架是安全、有效的。

Biological safety evaluation of 125I-filled carbon nanotubes covered with metallic esophageal stent

Objective To evaluate the biological safety of ¹²⁵I-filled carbon nanotubes covered with metallic esophageal stent with regard to the normal esophagus before clinical application. Methods ¹²⁵I-filled carbon nanotubes covered with metallic esophageal stent was prepared. Eighteen of New Zealand rabbits were randomly divided into three groups with 6 rabbits in each group. Three groups of stents, non-radioactive, low radio-activity(3.7-5.6 MBq), and high activity(11.1-13.0 MBq) were placed in the midpiece of esophagus of rabbits. Esophagus opacification and three-diamensions DSA were performed at 0.5 h, 7, 14 and 30 d after insertion of the stents, respectively. The rabbits were killed at 30 d after insertion of the stents, and histologic examinations of the esophageal walls were performed. Results In non-radioactive and low activity groups, 1 of 6 rabbits died of wound infection at 1 and 3 d after surgery due to pulmonary infection, respectively. All specimens were obtained from 16 rabbits. Microscopically, in all rabbits of low activity and high activity groups, there were membrana mucosa necrotic and swell and breakage of the muscle fiber in esophageal submucosa and muscularis, submucosal inflammation, which were more severe in high activity group. In low activity group, one esophagus ectal membrane was involved, however, esophageal perforation did not develop. In high activity group, 3 of 6 rabbits esophageal perforation had developed, in which one esophagus mediastinum fistula developed, without inflammation. In non-radioactive group, it was almost normal in mucosa layer, a small amount of inflammatory cells were found in submucosal layer, and part of muscle fibers was fractured and no pathological changes of necrosis was found. Conclusions Radioactive ¹²⁵I carbon nanotubes covered metallic stent with low activity(3.7-5.6 MBq) can be used as intraluminal palliative brachytherapy, which is safe and effective.