Anesthetic isoflurane posttreatment attenuates experimental lung injury by inhibiting inflammation and apoptosis.

Anesthetic isoflurane posttreatment attenuates experimental lung injury by inhibiting inflammation and apoptosis.
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DOI:
10.1155/2013/108928
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发表时间:
2013
影响因子:
4.6
通讯作者:
Gao CF
Gao CF
中科院分区:
医学3区
文献类型:
--
作者:
Li JT;Wang H;Li W;Wang LF;Hou LC;Mu JL;Liu X;Chen HJ;Xie KL;Li NL;Gao CF

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本实验研究了1.4%异氟醚(ISO)对zymosan (ZY)引起的小鼠炎症和细胞凋亡的影响。我们发现,在ISO处理后,zy挑战小鼠表现出明显的体重减轻,死亡率明显高,并且以组织病理学,组织学评分和干湿比恶化为特征的明显肺损伤。通过降低支气管肺泡灌洗液中总细胞、中性粒细胞和促炎细胞因子(即肿瘤坏死因子-α、白细胞介素- (IL-) 1β、IL-6和巨噬细胞炎性蛋白-2)的水平及其在肺组织中的mRNA表达,ISO显著减弱了zy诱导的肺中性粒细胞募集和炎症。ISO还能抑制zy诱导的肺组织核因子- kappab p65和诱导型一氧化氮合酶的表达和活化。ZY还导致肺组织中血红素加氧酶-1的表达和活性上调,并在ISO处理下进一步增强。此外,通过降低procaspase-8、procaspase-3、cleaved - caspase-8和cleaved - caspase-3的表达,以及caspase-3活性和bcl -2相关的X/ b细胞淋巴瘤2比值,ISO显著阻止zy诱导的小鼠肺细胞凋亡。这些结果表明,ISO是治疗zy诱导的肺损伤的潜在治疗药物,值得进一步研究。
We investigated the effect of 1.4% isoflurane (ISO) on the development of inflammation and apoptosis caused by zymosan (ZY) in mice. We found that ZY-challenged mice exhibited significant body weight loss, markedly high mortality, and significant lung injury characterized by the deterioration of histopathology, histologic scores, and wet-to-dry ratio after ISO treatment. ISO dramatically attenuated ZY-induced lung neutrophil recruitment and inflammation, as evidenced by the reduced levels of total cells, neutrophils, and proinflammatory cytokines (i.e., tumor necrosis factor-α, interleukin- (IL-) 1β, IL-6, and macrophage inflammatory protein-2) in bronchoalveolar lavage fluid and of their mRNA expression in lung tissues. ISO also inhibited ZY-induced expression and activation of nuclear factor-kappaB p65 and inducible nitric oxide synthase in pulmonary tissue. ZY administration also resulted in the upregulation of heme oxygenase-1 expression and activity in the lung, which was further enhanced by ISO treatment. Moreover, ISO markedly prevented ZY-induced pulmonary cell apoptosis in mice, as reflected by the decrease in expression of procaspase-8, procaspase-3, cleaved caspase-8, and cleaved caspase-3, as well as in caspase-3 activity and Bcl-2-associated X/B-cell lymphoma 2 ratio. These results indicate that ISO is a potential therapeutic drug for treating ZY-induced lung injury, and further investigations are warranted.
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