Kennedy-Feitosa Emanuel, Pinto Rômulo Fonseca Santos, Pires Karla Maria Pereira, Monteiro Ana Paula Teixeira, Machado Mariana Nascimento, Santos Juliana Carvalho, Ribeiro Marcelo Lima, Zin Walter Araújo, Canetti Cláudio Azevedo, Romana-Souza Bruna, Porto Luís Cristóvão, Valenca Samuel Santos
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Biochim Biophys Acta. 2014 Jan;1840(1):199-208. doi: 10.1016/j.bbagen.2013.09.028. Epub 2013 Sep 26.
Pulmonary emphysema is characterized by the loss of lung architecture. Our hypothesis is that the inhibition of 5-lipoxygenase (5-LO) production may be an important strategy to reduce inflammation, oxidative stress, and metalloproteinases in lung tissue resulting from cigarette smoke (CS)-induced emphysema.
5-LO knockout (129S2-Alox5(tm1Fun)/J) and wild-type (WT) mice (129S2/SvPas) were exposed to CS for 60days. Mice exposed to ambient air were used as Controls. Oxidative, inflammatory, and proteolytic markers were analyzed.
The alveolar diameter was decreased in CS 5-LO(-/-) mice when compared with the WT CS group. The CS exposure resulted in less pronounced pulmonary inflammation in the CS 5-LO(-/-) group. The CS 5-LO(-/-) group showed leukotriene B4 values comparable to those of the Control group. The expression of MMP-9 was decreased in the CS 5-LO(-/-) group when compared with the CS WT group. The expression of superoxide dismutase, catalase, and glutathione peroxidase were decreased in the CS 5-LO(-/-) group when compared with the Control group. The protein expression of nuclear factor (erythroid-derived 2)-like 2 was reduced in the CS 5-LO(-/-) group when compared to the CS WT group.
In conclusion, we show for the first time that 5-LO deficiency protects 129S2 mice against emphysema caused by CS. We suggest that the main mechanism of pathogenesis in this model involves the imbalance between proteases and antiproteases, particularly the association between MMP-9 and TIMP-1. General significance This study demonstrates the influence of 5-LO mediated oxidative stress, inflammation, and proteolytic markers in CS exposed mice.
肺气肿的特征是肺结构的丧失。我们的假设是，抑制5-脂氧合酶（5-LO）的产生可能是减少香烟烟雾（CS）诱导的肺气肿所致肺组织炎症、氧化应激和金属蛋白酶的重要策略。
将5-LO基因敲除（129S2-Alox5(tm1Fun)/J）和野生型（WT）小鼠（129S2/SvPas）暴露于CS中60天。将暴露于环境空气中的小鼠用作对照。分析氧化、炎症和蛋白水解标志物。
与WT CS组相比，CS 5-LO(-/-)小鼠的肺泡直径减小。CS暴露导致CS 5-LO(-/-)组的肺部炎症不那么明显。CS 5-LO(-/-)组的白三烯B4值与对照组相当。与CS WT组相比，CS 5-LO(-/-)组中MMP-9的表达降低。与对照组相比，CS 5-LO(-/-)组中超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的表达降低。与CS WT组相比，CS 5-LO(-/-)组中核因子（红细胞衍生2）样2的蛋白表达降低。
总之，我们首次表明5-LO缺乏可保护129S2小鼠免受CS引起的肺气肿。我们认为该模型发病机制的主要机制涉及蛋白酶和抗蛋白酶之间的失衡，特别是MMP-9和TIMP-1之间的关联。一般意义本研究证明了5-LO介导的氧化应激、炎症和蛋白水解标志物对暴露于CS的小鼠的影响。
