Activity and inhibition resistance of a phospholipase-resistant synthetic surfactant in rat lungs.
Activity and inhibition resistance of a phospholipase-resistant synthetic surfactant in rat lungs.
复制标题
大鼠肺中抗磷脂酶合成表面活性剂的活性和抑制抗性。
DOI：
10.1165/rcmb.2006-0434oc
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发表时间：
2007
影响因子：
6.4
通讯作者：
Notter,RobertH
中科院分区：
文献类型：
--
作者：
Wang,Zhengdong;Chang,Yusuo;Schwan,AdrianL;Notter,RobertH
本文研究了一种新型合成表面活性剂在大鼠肺中的活性和抗抑制性，该表面活性剂含有抗磷脂酶的二醚磷酸脂DEPN-8和1.5%牛表面活性剂蛋白(SP)-B/C，并与小牛肺表面活性剂提取物（CLSE）进行了比较。在磷脂酶A2（PLA2）或C18:1溶磷脂酰胆碱（LPC）存在的情况下，DEPN-8 + 1.5% SP-B/C在使表面活性剂缺乏的压力-体积（P-V）收缩机制正常化方面优于CLSE。在没有抑制剂或血清白蛋白存在的情况下，DEPN-8 + 1.5% SP-B/C在正常化P-V机制方面的活性与CLSE相等。这些生理活性的发现与脉动气泡表面计的表面活性测量结果直接一致。在没有抑制剂的情况下，DEPN-8 + 1.5% SP-B/C和CLSE迅速达到< 1 mN/m（0.5和2.5 mg表面活性剂磷脂/ml）的最小表面张力。DEPN-8 + 1.5% SP-B/C在PLA2存在下保持了较高的表面活性，而CLSE的表面活性受到PLA2的显著抑制。DEPN-8 + 1.5% SP-B/C在LPC存在下比CLSE具有更高的表面活性，两种表面活性剂在白蛋白存在下具有相当的表面活性。在脉动泡研究中，DEPN-8 + 1.5% SP-B/C暴露于过氧亚硝酸盐时，其表面活性也略高于CLSE。这些结果支持开发含有DEPN-8 +载脂蛋白/肽成分的高活性和抗抑制的合成外源性表面活性剂的潜力，用于治疗临床急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）的直接肺部形式。
This study investigates the activity and inhibition resistance in excised rat lungs of a novel synthetic surfactant containing the phospholipase-resistant diether phosphonolipid DEPN-8 plus 1.5% bovine surfactant protein (SP)-B/C compared to calf lung surfactant extract (CLSE). DEPN-8 + 1.5% SP-B/C surpassed CLSE in normalizing surfactant-deficient pressure–volume (P–V) deflation mechanics in lavaged excised lungs in the presence of phospholipase A2(PLA2) or C18:1 lyso-phosphatidylcholine (LPC). DEPN-8 + 1.5% SP-B/C had activity equal to CLSE in normalizing P–V mechanics in the absence of inhibitors or in the presence of serum albumin. These physiologic activity findings were directly consistent with surface activity measurements on the pulsating bubble surfactometer. In the absence of inhibitors, DEPN-8 + 1.5% SP-B/C and CLSE rapidly reached minimum surface tensions < 1 mN/m (0.5 and 2.5 mg surfactant phospholipid/ml). DEPN-8 + 1.5% SP-B/C maintained its high surface activity in the presence of PLA2, while the surface activity of CLSE was significantly inhibited by exposure to this enzyme. DEPN-8 + 1.5% SP-B/C also had greater surface activity than CLSE in the presence of LPC, and the two surfactants had equivalent surface activity in the presence of albumin. DEPN-8 + 1.5% SP-B/C also had slightly greater surface activity than CLSE when exposed to peroxynitrite in pulsating bubble studies. These results support the potential of developing highly active and inhibition-resistant synthetic exogenous surfactants containing DEPN-8 + apoprotein/peptide constituents for use in treating direct pulmonary forms of clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS).