【摘要】 肺气肿是终末细支气管至肺泡内持续含气量过多、过度膨胀使弹力组织破坏的常见慢性阻塞性肺疾病,临床表现为不可逆气流受限、胸闷、气促、重则呼吸衰竭.通过栓塞支气管使肺不张以达到肺减容目的的治疗方法因其能够避免外科手术风险而被广泛关注.本研究的目的是基于具有良好生物相容性的壳聚糖水凝胶制备一种可注射的原位水凝胶,考察该体系的凝胶时间、凝胶强度及细胞毒性等,并将其应用于肺栓塞以达到肺减容.研究结果表明,壳聚糖/京尼平/磷酸钠原位可注射水凝胶的凝胶时间为8 min,凝胶强度195 Pa,在生理条件下膨胀率超过100%;小鼠成纤维细胞(3T3)与凝胶接触48 h后细胞活性仍保持80%以上,表明凝胶无生物毒性;将该水凝胶注射入狗的肺细支气管,胸部CT显示水凝胶在定位的细支气管中形成栓塞,3周后在支气管肺段发生了局部肺不张,达到了肺减容的目的.更多还原

【Abstract】 Biological lung volume reduction(BLVR)using lung sealant has received more attention recently as a new non-surgical approach to emphysema treatment. Many tissue sealants have been studied but only a few have been proposed for BLVR. In this work, we prepared in situ forming chitosan-based hydrogels(CSG) using covalent cross-linking of chitosan and genipin in the cooperation of ionic interaction between chitosan and sodium orthophosphate hydrate(Na3PO4 12H2O) and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and rheological methods. CSG showed short gelation time(8 min), high swelling ratio([100 %) and non-toxicity(3T3 mouse fibroblast cell viability [80 %)under physiological conditions. The application of lung sealant for BLVR was tested in a Chinese dog and evaluated by chest computed tomography. After 3 weeks of the installation of CSG in bronchopulmonary segment, the gel formation was detected at a localized region of bronchi and the local atelectasis occurred. Our findings indicate thatthis chitosan-based hydrogel is a promising new candidate for use as a lung sealant for BLVR.更多还原