Protective mechanisms of sevoflurane against one-lung ventilation-induced acute lung injury: role of cyclooxygenase-2 and 5-lipoxygenase pathways

南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (05): 625-.

Protective mechanisms of sevoflurane against one-lung ventilation-induced acute lung injury: role of cyclooxygenase-2 and 5-lipoxygenase pathways

刘睿，罗静，李江，马庆杰，李艳华，王殿华

出版日期:2013-05-20 发布日期:2013-05-20

从COX2和5-LOX途径探讨七氟醚抗单肺通气致急性肺损伤的作用机制

Online:2013-05-20 Published:2013-05-20

摘要/Abstract

摘要： 目的从COX2和5-LOX途径探讨七氟醚抗单肺通气致急性肺损伤作用机制。方法18只健康日本大耳白兔随机分为假手
术组（S组），单肺通气组（O组），单肺通气+七氟醚组（OS组），每组6只。用Western blotting和定量RT-PCR分别检测肺组织环
氧化酶-2（COX2）、5-脂氧化酶（5-LOX）蛋白和mRNA表达水平。ELISA检测肺组织白细胞三烯B4（LTB4）、血栓素A2（TXA2）和
前列腺素I2（PGI2）含量。以肺湿/干（W/D）比值和肺组织学评分评价肺损伤的严重程度。结果与S组相比，O组和OS组动物肺
组织COX2、5-LOX蛋白和mRNA表达水平，LTB4、TXA2、PGI2含量，肺W/D比值及肺组织学评分均明显升高（P<0.05），而肺组
织PGI2/TXA2比值明显降低（P<0.05）。与O组相比，OS组肺组织PGI2/TXA2比值明显增高（P<0.05），而其它各项指标均明显降
低（P<0.05）。结论本研究首次证实单肺通气可使实验动物肺组织COX2、5-LOX的蛋白和mRNA表达水平增高。七氟醚具有
抗单肺通气致急性肺损伤的作用，其机制可能与下调肺组织COX2和5-LOX的表达水平，减少肺组织PGI2、TXA2和LTB4生成及
调控PGI2/TXA2比值有关。

Abstract: Objective To explore the protective mechanisms of sevoflurane against acute lung injury (ALI) induced by one-lung
ventilation (OLV) in view of cyclooxygenase-2 (COX2) and 5-lipoxygenase (5-LOX) pathways. Method Eighteen healthy
Japanese white rabbits were randomized into sham-operated group (S group), OLV group (O group) and OLV + sevoflurane
group (OS group). COX2 and 5-LOX protein and mRNA expressions in the lungs were detected by Western blotting and
real-time PCR, respectively. Prostaglandin I2 (PGI2), thromboxane A2 (TXA2) and leukotrienes B4 (LTB4) in the lung tissues were
quantified with ELISA. Histological scores and lung wet/dry weight (W/D) ratios were determined for lung injury assessment.
Results COX2 and 5-LOX protein and mRNA expressions and the contents of LTB4, TXA2 and PGI2 in the lungs, lung W/D ratio
and histological scores were significantly higher while PGI2/TXA2 ratio was significantly lower in O group and OS group than
in S group (P<0.05). Compared with those in O group, COX2 and 5-LOX expressions, pulmonary contents of LTB4, TXA2 and
PGI2, and lung W/D ratio all decreased significantly but PGI2/TXA2 ratio was significantly elevated in OS group (P<0.05).
Conclusion OLV may activate COX2 and 5-LOX pathways to result in increased production of arachidonic acid metabolites.
Sevoflurane protects against OLV-induced ALI probably by reducing AA metabolites and regulating PGI2/TXA2 ratio through
inhibitions of COX2 and 5-LOX pathways.

刘睿，罗静，李江，马庆杰，李艳华，王殿华. Protective mechanisms of sevoflurane against one-lung ventilation-induced acute lung injury: role of cyclooxygenase-2 and 5-lipoxygenase pathways[J]. 南方医科大学学报, 2013, 33(05): 625-.