摘要
目的从COX_2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(COX_2)、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B_4(LTB_4)、血栓素A_2(TXA_2)和前列腺素I_2(PGI_2)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COX_2、5-LOX蛋白和mRNA表达水平,LTB_4、TXA_2、PGI_2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PGI_2/TXA_2比值明显降低(P<0.05)。与O组相比,OS组肺组织PGI_2/TXA_2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COX_2、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COX_2和5-LOX的表达水平,减少肺组织PGI_2、TXA_2和LTB_4生成及调控PGI_2/TXA_2比值有关。
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 5-1ipoxygenase (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 L (PGL), thromboxane A2 (TXA2) and leukotrienes B4 (LTB0 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 LTBo TXA2 and PGIa in the lungs, lung W/D ratio and histological scores were significantly higher while PGIdTXA2 ratio was significantly lower in O group and OS group than in S group (P〈0.05). Compared with those in O group, COXa and 5-LOX expressions, pulmonary contents of LTB4, TXA2 and PGI2, and lung W/D ratio all decreased significantly but PGIdTXA2 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 PGIdTXA2 ratio through inhibitions of COX2 and 5-LOX pathways.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2013年第5期625-630,共6页
Journal of Southern Medical University
基金
Supported by National Natural Science Foundation of China(30840043)~~
关键词
单肺通气
七氟醚
环氧化酶
2
5
脂氧化酶
one-lung ventilation
sevoflurane
cyclooxygenase-2
5-1ipoxygenase