Development of inhibitor-resistant lung surfactant

在ARDS中，表面活性剂抑制剂出现并引起呼吸衰竭。在开发耐腐蚀表面活性剂的研究中，获得了以下结果。(I)多糖（葡聚糖）的作用。(1)将右旋糖酐（40- 70 kDa）加入到表面活性剂和血清（表面活性剂抑制剂）的混合物中，可逆转受抑制的活性，增加未成熟新生兔的潮气量。(2)在ARDS大鼠中，雾化吸入表面活性物质后雾化吸入右旋糖酐明显优于单独雾化吸入表面活性物质。(3)右旋糖酐可降低胎粪对表面活性物质的抑制作用，提示其对胎粪吸入综合征有治疗作用。(II)调节表面活性剂蛋白。(1)用由合成磷脂和不同剂量的表面活性蛋白B和C（SP-B和SP-C）组成的重建表面活性剂治疗ARDS大鼠。结果表明，当SP-B和SP-C分别大于0.7%和1.4%时，重组表面活性剂才能发挥治疗作用。(2)分子结构中缺少棕榈酰基的SP-C单体（Monomeric form of SP-C，mSP-C）并不能改善其生理功能，而多聚体（polymer form of mSP-C）的生理功能优于正常SP-C。(III)其他研究。(1)在幼兔，呼气末正压可逆转血清对肺表面活性物质的抑制作用。(2)表面活性剂替代逆转了吸入织物保护剂引起的呼吸衰竭。(3)异丙酚减少炎症反应。

In ARDS, surfactant inhibitors appear and cause respiratory failure. In studies to develop an inhibitor-resistant surfactant, the following results were obtained.(I) Effects of polysaccharides (dextran). (1) Addition of dextran (40-70kDa) to a mixture of surfactant and serum (a surfactant inhibitor) reversed the inhibited activity and increased tidal volumes of immature newborn rabbits. (2) In rats with ARDS, inhalation of aerosolized surfactant followed by aerosolized dextran improved the lung functions significantly better than that of aerosolized surfactant alone. (3) Dextran reduced surfactant inhibition by meconium, suggesting the therapeutic effects on meconium aspiration syndrome.(II) Modulation of surfactant proteins. (1) ARDS rats were treated with reconstituted surfactants consisted of synthetic phospholipids plus various doses of surfactant proteins B and C (SP-B ＆ SP-C). It was demonstrated that >0.7% in SP-B and >1.4% in SP-C were needed for the reconstituted surfactant to bring about the therapeutic effects. (2) Monomeric form of SP-C (mSP-C) which lacks palmitoyl radical in the molecular structure does not improve the physiologic function, but polymeric form of mSP-C shows the physiologic function better than normal SP-C.An application of polymeric form of mSP-C was strongly suggested for development of artificial surfactant to treat ARDS patients.(III) Additional studies. (1) In immature rabbits, positive end-expiratory pressure reversed serum-inhibited function of lung surfactant. (2) Surfactant replacement reversed respiratory failure caused by inhalation of fabric protector. (3) Propofol reduced inflamatory responses.