Basic research and development of de novo-designed peptide/fluorinated carbon hybrid artificial lung surfactant

本研究旨在研究人表面活性物质蛋白B的模拟多肽(Hel/3-5)在磷脂(DPPC)和不同的脂质混合物中的界面行为，并考察人工表面活性物质制剂的体外表面活性与体内肺功能的相关性。新的发现如下：I：DPPC本身在肺功能方面存在一些缺陷，如快速再扩散、吸附和大滞后。然而，加入少量的He113-5使DPPC的吸附性能得到改善，DPPC的表面压力(π)-面积(A)曲线的滞后性可逆地增大，显示出替代SP-B的作用。II：添加剂PG选择性地起作用，在挤出过程中与阳离子HEL13-5发生静电作用，然后含有HEL13-5的三维聚集体在表面单分子层正下方形成。这种形成有助于DPPC单分子膜的稳定性。另一方面，功放组件不是主要的Squee…更多的表面单层与He113-5一起剥离，并与DPPC在界面形成紧密堆积的单层。III：人工制剂和Surfacten(RDS患者可买到的)的表面化学(Langmuir等温线、荧光图像、温度依赖性和滞后曲线)进行了比较。最重要的是，该人工制剂在表面活性和界面行为方面与Surfacten相当。IV：在体内，该制剂的有效性在大鼠肺和表面活性物质缺乏的大鼠中得到阐明。含2.5wt%Hel13-5的制剂用于动态肺顺应性和准静态压力-体积曲线的活体测量。2.5wt%Hel13-5制剂在改善肺表面活性物质缺乏大鼠的肺功能和机械性能方面与表面活性物质相当，最终，这种肺表面活性物质替代品将有助于使表面活性物质制剂适应表面活性物质缺乏、不足和失活的不同状态。较少

This study is aimed to investigate the interfacial behavior of a mimic peptide (Hel/3-5) of human surfactant protein B, in a phospholipid (DPPC) and various lipid mixtures and to examine the correlation between in vitro surface activity and in vivo lung function of artificial surfactant preparation. The new finding is following terms.I: DPPC alone has some defects in pulmonary functions such as rapid respreading, adsorption, and large hysteresis. However, addition of a small amount of He113-5 to DPPC led to improvement in adsorption of DPPC, and enlargement of a hysteresis of surface pressure (π)-area (A) curve for DPPC reversibly, as shown a substitute for SP-B.II: Additive PG works selectively and electrostatically interact with cationic Hel13-5 during the squeeze-out process and then 3-D aggregates containing Hel13-5 and being formed just below the surface monolayer. This formation contributes to the stability of DPPC monolayers. On the other hand, PA components are not mainly squee … More zed out of surface monolayers together with He113-5, and form the close-packed monolayer with DPPC at the interface.III: Surface chemistry (Langmuir isotherms, fluorescent images, temperature dependence, and hysteresis curves) of the artificial preparation and Surfacten (commercially available for RDS patients) has been made for the comparison between them. Above all, this artificial preparation is comparative to Surfacten in terms of surface activity and the interfacial behavior.IV: In vivo, efficacy of this preparation was elucidated in a rat lung and a surfactant-deficient rat. The preparations containing 2.5wt% Hel13-5 was used for the in vivo measurements of dynamic lung compliances and quasi-static pressure-volume curves. The preparation with 2.5wt% Hel13-5 was equivalent to Surfacten with respect to improving lung function and mechanics for the surfactant-deficient rat.Finally, this pulmonary surfactant substitutes will contribute to tailoring surfactant preparations to various states of surfactant deficiency, insufficiency and inactivation. Less