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。在开发抗抑制剂表面活性剂的研究中，得到了以下结果。(1)多糖（葡聚糖）的作用。(1)在表面活性剂和血清（一种表面活性剂抑制剂）的混合物中加入葡聚糖（40-70kDa），逆转了未成熟新生兔的抑制活性，增加了潮气量。(2)急性呼吸窘迫综合征大鼠吸入表面活性剂雾化后再雾化右旋糖酐对肺功能的改善明显优于单独雾化表面活性剂。(3)右旋糖酐降低胎粪对表面活性剂的抑制作用，提示对胎粪吸入综合征有治疗作用。（II）表面活性剂蛋白的调节。(1)用合成磷脂加不同剂量表面活性剂蛋白B和C （SP-B和SP-C）组成的重组表面活性剂治疗ARDS大鼠。结果表明，复合表面活性剂在SP-B和SP-C中分别需用>0.7%和>1.4%才能达到治疗效果。(2)单体形态的SP-C （mSP-C）在分子结构上缺乏棕榈酰自由基，对生理功能没有改善作用，但聚合形态的SP-C表现出比正常SP-C更好的生理功能。建议将聚合形式的mSP-C应用于开发治疗ARDS的人工表面活性剂。（三）进一步研究。(1)未成熟家兔呼气末正压可逆转肺表面活性剂的血清抑制功能。(2)表面活性剂替代可逆转吸入织物保护器引起的呼吸衰竭。(3)异丙酚降低炎症反应。

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.