Alda-1通过激活线粒体乙醛脱氢酶2改善大鼠肺缺血再灌注损伤

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摘要目的：通过Alda-1激活线粒体乙醛脱氢酶2（ALDH2）活性，探讨激活该酶对大鼠肺缺血再灌注损伤的保护作用。方法：选择24只SD雄性大鼠，随机分为假手术组（Sham组）、缺血再灌注组（I/R组）和Alda-1+缺血再灌注组（Alda-1组）。实验结束取肺组织和动脉血标本，测各组肺组织的湿干重比（W/D）、HE染色观察肺泡结构；检测血浆及肺组织的丙二醛（MDA）含量、4-羟基壬烯醛（4-HNE）浓度；Western blot检测ALDH2的相对表达量及ELISA检测ALDH2的活性。结果：与Sham组相比，I/R组肺组织W/D值明显升高（P＜0.05），肺泡结构明显破坏，血浆及肺组织的MDA、4-HNE明显增多（P＜0.05），ALDH2的活性明显降低（P＜0.05）；与I/R组相比，Alda-1组肺组织W/D值显著下降（P＜0.05），肺泡结构显著改善，血浆及肺组织的MDA、4-HNE显著减少（P＜0.05），ALDH2的活性明显升高（P＜0.05）。结论：Alda-1可通过激活ALDH2的活性来加速醛类物质代谢从而减轻肺缺血再灌注损伤。

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关键词 ：肺, 再灌注损伤, Alda-1, 乙醛脱氢酶2, 丙二醛, 4-羟基壬烯醛

Abstract：Objective: To investigate the protective effect of Alda-1 activated mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) on lung ischemia-reperfusion injury (LIRI) in rats. Methods: Twenty-four SD male rats were randomly divided as sham operation group (Sham group), ischemia-reperfusion group (I/R group) and Alda-1+ischemia-reperfusion group (Alda-1 group). The lung tissue and arterial blood samples were taken at the end of the experiment. The wet-to-dry weight ratio (W/D) of the lung tissue was measured; the alveolar structure was observed by HE staining; the malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) in plasma and lung tissue were detected; the content of ALDH2 was determined by Western blot and the activity of ALDH2 by ELISA. Results: Compared with the Sham group, the I/R group showed that the W/D value was significantly increased (P<0.05), the alveolar structure markedly destroyed, MDA and 4-HNE in the plasma and lung tissues remarkably improved (P<0.05), the activity of ALDH2 signally decreased (P<0.05). However, in the Alda-1 group, the W/D value was significantly decreased (P<0.05), the alveolar structure markedly improved, the MDA and 4-HNE of plasma and lung tissues remarkably decreased (P<0.05), and the activity of ALDH2 signally improved (P<0.05), compared with the I/R group. Conclusion: Alda-1 can accelerate the metabolism of aldehydes by activating ALDH2 to improve lung ischemia-reperfusion injury.

Key words： lung reperfusion injury Alda-1 acetaldehyde dehydrogenase 2 malondialdehyde 4-hydroxy-nonenal

收稿日期: 2019-02-16

基金资助:温州市科技计划项目（Y20160371）。

通讯作者: 刘乐，副主任医师，Email：lle2@163.com。

作者简介: 张裕坚（1984-），男，福建古田人，主治医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2019/V49/I10/744

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