高分子聚合物逆转血浆所致肺表面活性物质失活

Polymers reverse inactivation of surfactant induced by plasma

目的包括血浆在内的许多物质能够抑制肺表面活性物质（PS）降低表面张力的能力，这是急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）的重要病理改变之一。本研究的目的是探讨高分子聚合物是否可以防止或减轻血浆诱导的Ps失活。方法利用闭泡式表面张力仪分别测量葡聚糖（dextran）、聚乙二醇（PEG）和透明质酸（HA）、PS（固尔苏，curosurf）以及加入了1％～3％血浆的混合物最大表面张力（γmax）和最小表面张力（γmin），并计算它们的稳定系数（SI）。结果不同高分子聚合物、血浆及它们的混合物γmin均〉10mN／m，SI〈0．8，而curosurf（1．25mg／ml）的γmin为（1．54±0．03）mN／m，SI为1．71±0．01。Curosurf与1％、2％或3％的血浆混合后γmin分别为（19．0±0．46）mN／m、（22．9±0．42）mN／m和（22．6±1．22）mN／m，SI为0．38±0．05、0．34±0．02和0．39±0．15。 述混合物与5％PEG、5％dextran或0．25％HA混合，γmin分别降至（1．59±0．22）mN／m、（1．43±0．24）mN／m、（17．2±0．72）mN／m；（0．88±0．06）mN／m、（1．18±0．06）mN／m、（1．46±0．22）mN／m及（1．22±0．10）mN／m、（1．33±0．07）mN／m、（1．42±0．18）mN／m，与curosurf同各浓度血浆混合物比较，差异均有统计学意义（P均〈0．05）。S1分别增加到1，72±0．04、1．73±0．04、0．43±0．04；1．82±0．01、1．82±0．01、1．79±0．03及1．79±0．02、1．79±0．01、1．79±0．04，与curosurf同各浓度血浆混合物比较，差异均有统计学意义（P均〈0．05）。不同浓度的高分子聚合物显著提高了血浆存在情况下curosurf降低γmin、增加SI的能力（rPEG=-0．718，P〈0．01；rdextran=-0．682，P〈0．01；rHA=-0．889，P〈0．01）。结论高分子聚合物可以逆转血浆所致的curosurf失活，和PEG比较，dextran和HA与curosurf联合应用可以更好地对抗血浆的抑制。

Objective Objective A variety of substances including plasma have been found to affect adversely the surface tension-lowering activity of pulmonary surfactant, and this effect may be important in the pathogenesis of a number of human diseases such as acute lung injury（ALI） and acute respiratory distress syndrome（ ARDS）. We were aimed at exploring whether inactivation of surfactant induced by plasma could be prevented or reduced by polymers. Methods We measured the maximum （γmax） and minimum sueface tension （ γmin ） of dextran, polyethylene glycol （PEG）, hyaluronan（HA）, pulmonary surfactant（ Curosurf）, plasma and their mixtures by captive bubble surfactometer, respectively. Values of stability index（S. I. ） were also calculated. Results The γmin of different polymers, plasma and their mixtures were more than 10 mN/m and S. I. of which were less than 0.8. The γmin and S. I. of Curosurf（ 1.25 mg/ ml） were （1.54± 0.03）mN/m and 1.71 ± 0.01, respectively. The rain and S. I. of Curosurf mixed with 1% ,2% or 3% plasma were（ 19.0 ± 0.46） mN/m, （22.9 ± 0.42） mN/m and（22.6 ± 1.22） mN/m and 0.38 ± 0.05,0.34 ± 0.02 and0.39 ± 0.15, respectively. When mixed with 5% PEG, 5% dextran and 0.25% HA, the γmin significantly decreased to[ （1.59 ± 0.22）mN/m, （1.43 ± 0.24） mN/m, （ 17.2 ± 0.72）mN/m; （0.88 ± 0. （36）mN/m, （ 1.18 ± 0.（36）mN/m, （1.46±0.22）mN/m and （1.22 ± 0.10 ）mN/m, （1.33 ± 0.07 ）mN/m, （1.42 ± 0.18 ）mN/m,respectively, （ P 〈 0.05 ） ,and the S. I. significantly increasedto to 1.72 ± 0. 04,1.73 ±0. 04,0.43 ±0.04;1.82±0.01 ,1.79±0.03 and 1.79±0.02,1.79±0.01,1.79±0.04 respectively, （ P 〈 0.05 ）. Different concentrations of polymers significantly enhanced the ability of Curosurf in reducing the γmin and elevating S. I. in the presence of plasma. Conclusion PoIymers are capable of reversing inactivation of surfactant induced by plasma in vitro. The data suggests that dextran and HA be more effective to lower the γmin than PEG when mixed with Curosurf.