活化多形核白细胞及其弹性蛋白酶对大鼠肺的损伤作用

The Damaging Effect of Actirated Human Neutrophils on Isolated Perfused Rat Lungs The Role of Elastase

本研究观察了活化多形核白细胞（ＰＭＮ）及其弹性蛋白酶（ＨＮＥ）对大鼠灌流肺的损伤作用。发现ＰＭＮ被佛波酯（ＰＭＡ）激活后３０、６０ｍｉｎ灌流液中ＨＮＥ有显著性增加。ＰＭＮ以Ａ２３１８７，活化后１０ｍｉｎ灌流液中ＨＮＥ即显著升高（Ｐ＜０．０５），并维持在高水平。该组肺泡灌洗液中ＨＮＥ和白蛋白含量也有显著增加（Ｐ＜０．０５）。结果提示ＰＭＮ激活后可导致肺损伤，其释放的弹性蛋白酶是损伤的因素之一。

Human neutrophil and its elastase play an important role in the pathogenesis of various lung diseases.We investigated the damaging effect of human neutrophils stimulated with PMA(phorbol myristate acetate 10ng/ml)or calcium ionophase A23l87(2ng/ml)on isolated perfused rat lungs.The study specimens consisted of 4 groups of animals.A control,B perfused with human neutrophils,C perfused with human neutrophils stimulated with PMA,and D perfused with human neutrophils stimulated with A23187.By using the ELISAmethod,we found that the level of human neutrophil elastase(HNE)in perfusate increasedsignificantly at 30min(1.68±0.79ng/ml P<0.05)and 60min(2.35±0.87ng/ml P<0.01)after PMA stimuating,but the HNE in the lung lavage fluid of the same group only slightly increasedand the concentration of protein in lavage fluid did not change.After stimulating with A23187,the concentration of HNE in perfusate increased markedly at 30min(4.03±1.96ng/ml P<0.01)and maintained at high level(P<0.01).There was a significant increase of HNE level in lung lavage fluid(2.49±0.61ng/ml)from group D rat lungs,compared with group A,B or C,and the protein as well(1.61±0.58mg/ml P<0.05).All the results indicate that the stimulated human neutrophils can release elastase in perfused rat lung.Neutrophil stimulated with A23187 can increase pulmonary permeability and injure the lung.We suggest that the lung damage,caused by human neutrophils,may be the effect of neutrophil elastase or the synergistic effect with some other substances derived from neutrophil.