Effect of the NADPH oxidase inhibitor apocynin on septic lung injury in guinea pigs.
Effect of the NADPH oxidase inhibitor apocynin on septic lung injury in guinea pigs.
复制标题
NADPH 氧化酶抑制剂罗布麻宁对豚鼠脓毒性肺损伤的影响。
DOI：
10.1164/ajrccm.150.5.7952574
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发表时间：
1994
影响因子：
24.7
通讯作者：
Raffin,TA
中科院分区：
文献类型：
--
作者：
Wang,W;Suzuki,Y;Tanigaki,T;Rank,DR;Raffin,TA
中性粒细胞中NADPH氧化酶活化产生的活性氧在脓毒症诱导的急性肺损伤中起主要作用。为了深入了解NADPH氧化酶抑制剂夹竹桃麻素是否可以减轻氧化剂诱导的肺损伤，我们检查了夹竹桃麻素对（1）豚鼠脓毒症诱导的肺损伤，（2）通过化学发光（CL）测量的LPS刺激的中性粒细胞产生的ROS，和（3）通过51 Cr释放评估的LPS刺激的嗜中性粒细胞介导的人脐静脉内皮细胞（HUVEC）损伤的影响。通过比较肺组织和支气管肺泡灌洗液（BAL）中相对于血浆的125 I标记白蛋白浓度（L/P和BAL/P）、肺湿干重比和BAL液中中性粒细胞数量，评估豚鼠脓毒症诱导的肺损伤。在用夹竹桃麻素预处理和后处理后，肺湿/干重比、L/P和BAL液中中性粒细胞数目降低。BAL/P降低预处理后，但不后与夹竹桃麻素治疗。浓度为10至100微克/ml的夹竹桃麻素显著降低LPS刺激的中性粒细胞CL和嗜中性粒细胞介导的HUVEC 51 Cr释放。我们的结论是，NADPH氧化酶抑制剂夹竹桃苷减轻（1）豚鼠脓毒症诱导的肺损伤，（2）中性粒细胞ROS的产生（CL测量），（3）嗜中性粒细胞介导的HUVEC损伤（51 Cr释放评估）。
Reactive oxygen species (ROS) produced by NADPH oxidase activation in neutrophils play a major role in mediating sepsis-induced acute lung injury. To provide insight into whether the NADPH oxidase inhibitor apocynin might attenuate oxidant-induced lung injury, we examined the effect of apocynin on (1) sepsis-induced lung injury in guinea pigs, (2) ROS generation by LPS-stimulated neutrophils measured by chemiluminescence (CL), and (3) LPS-stimulated neutrophil-mediated human umbilical vein endothelial cell (HUVEC) injury assessed by 51Cr release. Sepsis-induced lung injury in guinea pigs was assessed by comparing 125I-labeled albumin concentrations in lung tissue and bronchoalveolar lavage (BAL) fluid relative to plasma (L/P and BAL/P), lung wet-to-dry weight ratios, and the number of neutrophils in BAL fluid. The lung wet-to-dry weight ratio, L/P, and the number of neutrophils in BAL fluid decreased after pretreatment and post-treatment with apocynin. BAL/P decreased upon pretreatment but not upon post-treatment with apocynin. Apocynin at concentrations from 10 to 100 micrograms/ml significantly reduced LPS-stimulated neutrophil CL and neutrophil-mediated HUVEC 51Cr release. We conclude that the NADPH oxidase inhibitor apocynin attenuates (1) sepsis-induced lung injury in guinea pigs, (2) neutrophil ROS generation measured by CL, and (3) neutrophil-mediated HUVEC injury assessed by 51Cr release.