人工肺表面活性物质作为全氟碳化合物肺部给氧载体的研究

The partial pressure of oxygen in ambient air is the driving force of the oxygen from the lung into the arterial blood, and further into individual cells of the body. When the partial pressure of oxygen is decreased, the hypoxia symptoms in body would occur, which is harmful to the various systems of the body in different degree. The present equipments of supplying oxygen for hypoxia only focus on the supplying concentration of oxygen, and always ignore the oxygen utilization by lung. Therefore, based on our preliminary work, we will develop a novel series of nanoemulsions with artificial pulmonary surfactant (APS) and perfluorocarbon (PFC) through APS using as a carrier for PFC. The novel series of nanoemulsions, labeled as PFC-APS nanoemulsions, can supply oxygen to lung through pulmonary delivery. The reasons are those as following: PFC can dissolve oxygen, decrease alveolar surface tension effectively and increase the compliance of the lung, which makes dissolved oxygen access to the pulmonary vascular easily. On the other hand, because of the similar properties between APS and natural pulmonary surfactant, APS can extend atelectasis region to help PFC to obtain more uniform intrapulmonary distribution, avoid alveolar collapse and improve pulmonary gas exchange capacity. Thus, PFC-APS nanoemulsions are taken into account not only the concentration of oxygen supply but also the oxygen utilization of lung. To our best understand, the results of project have potential usage for portable and efficient supplying oxygen equipment in future.

环境空气中氧气的分压是氧气由肺脏进入动脉血而最终分布到全身各个细胞的原动力。当氧分压下降时，机体就会出现缺氧症状。这会对人体各系统将产生不同程度的影响。目前用于缺氧急救的供氧方式只考虑到氧气供给浓度，未考虑到肺脏对氧气的利用率。本项目在前期工作的基础上，拟采用人工肺表面活性物质（APS）包裹具有高携氧性的全氟碳化合物（PFC），制备PFC-APS乳剂，通过肺部给药，用于体内供氧。PFC不仅具有高溶氧性能，而且可降低肺泡表面张力，增加肺脏的顺应性，使得溶解氧易于进入肺血管。同时，利用APS与天然肺表面活性物质相似的性质，扩展肺膨胀不全的区域，帮助PFC获得更为均一的肺内分布，保证呼气时肺泡不至萎陷，提高肺部气体交换能力。因此，PFC-APS乳剂既考虑到氧气供给浓度，又考虑到肺脏对氧气的利用率。本项目的完成对开发便携式、高效供氧设备具有理论指导意义。

环境空气中氧气的分压是氧气由肺脏进入动脉血而最终分布到全身各个细胞的原动力。当氧分压下降时，机体就会出现缺氧症状。这会对人体各系统将产生不同程度的影响。目前用于缺氧急救的供氧方式只考虑到氧气供给浓度，未考虑到肺脏对氧气的利用率。本项目以常用的人工肺表面活性物质——DPPC材料为载体，制备得到DPPC-PFOB乳剂，并进行细胞实验。发现不论是在低氧还是正常氧条件下都能够促进细胞的生长，在缺氧-复氧条件下，也能够有效缓解细胞缺氧状态，使得细胞能够恢复到正常状态。对DPPC-PFOB乳剂进行动物实验，分别建立了急性呼吸窘迫症模型与全肺关系模型，实验结果证明复合乳剂能够有效提高肺部顺应性，提高血氧浓度并且降低肺部炎症程度，其中复合乳剂中DPPC在提高肺顺应性上起到了关键性作用。本项目按照计划完成了既定的研究内容，达到了预期的研究目标；同时在原有研究内容基础上，探讨了APS对缺氧恢复的机制，开发出缺氧快速缓解的喷雾剂样件。本项目的完成累计发表文章4篇；申请专利3项，授权专利2项；培养上海市启明星计划获得者1名，研究生3名；获得上海市闵行区科技进步二等奖1项。