[Changes and significance of autophagy in rat lung injury induced by gas explosion]

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2021 Aug 20;39(8):568-573. doi: 10.3760/cma.j.cn121094-20201010-00568.
[Article in Chinese]

Abstract

Objective: To explore the changes and significance of autophagy in acute lung injury (ALI) induced by gas explosion in rats. Methods: In February 2018, the gas explosion in underground coal mine was simulated by large tunnel explosion experiment system, SD rats were randomly divided into control group and 6 distance groups (40 m, 80 m, 120 m, 160 m, 200 m, 240 m) with 18 rats in each group. The respiratory function of rats 24 h before and after explosion was detected. Post-explosion rats were anesthetized and sacrificed, histopathological changes of lung were observed by HE staining. Immunohistochemistry was performed to detect the in situ expression of autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3B) . The expression levels of autophagy related gene 12 (Atg12) , LC3B, P62, lysosomal associated membrane protein 2 (Lamp2) , B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl2 interaction protein (Beclin-1) were detected by Western blot. Results: After gas explosion, the rats in 80 m distance point group had the hightest mortality (n=13, 72.22%) and the most severe lung injury degree, and the histopathological scores was (4.00±0.00) point. After gas explosion, the minute ventilation volume (MVb) , maximum inspiratory flow rate (PIFb) and maximum expiratory flow rate (PEFb) of rats were lower than before the gas explosion (P<0.05) . The respiratory frequency of rats in 80 m, 200 m, and 240 m distance point groups were significantly higher than that in the control group (P<0.05) . The expression levels of LC3B in 40 m, 80 m, 120 m, 160 m, and 200 m distance point groups were higher than that in the control group (P<0.05) . The relative expression levels of Atg12 and LC3BⅡ/Ⅰ in lung tissues of rats in different distance point groups were higher than those in the control group (P<0.05) . The relative expression levels of Beclin1 in 40 m, 80 m, 120 m, and 160 m distance point groups were significantly higher than that in the control group (P<0.05) . The relative expression levels of P62 in 80 m, 160 m and 200 m distance point groups were lower than that in the control group (P<0.05) . The relative expression levels of Lamp2 and Bcl-2 in lung tissues of rats in all distance groups except 240 m distance group were lower than those in the control group (P<0.05) . Conclusion: Gas explosion could induce increased autophagy in lung tissues of ALI rats. Autophagy-related signaling pathway could be involved in the pathophysiological process of ALI in rats caused by gas explosion, then the autophagy and the severity of the lesion showed a significant positive correlation.

目的: 探索细胞自噬在瓦斯爆炸致大鼠急性肺损伤(ALI)中的改变及其意义。 方法: 于2018年2月,通过大型巷道爆炸实验系统模拟煤矿井下瓦斯爆炸,将SD大鼠随机分为对照组以及6个距离组(40 m、80 m、120 m、160 m、200 m、240 m),每组18只。于爆炸前、爆炸后24 h检测各组大鼠呼吸功能,麻醉处死大鼠后,通过HE染色观察肺组织病理学变化;免疫组化检测自噬标志蛋白B型微管相关蛋白1轻链-3(LC3B)原位表达情况;Western blot检测自噬相关基因12(Atg12)、LC3B、P62、溶酶体相关膜蛋白2(Lamp2)、B细胞淋巴瘤/白血病-2蛋白(Bcl-2)和Bcl-2相互作用蛋白(Beclin-1)的表达水平。 结果: 瓦斯爆炸后,80 m距离组大鼠死亡率最高(13只,72.22%),肺组织损伤程度最严重,组织病理学评分为(4.00±0.00)分。瓦斯爆炸后,大鼠每分通气量(MVb)、最大吸气流速(PIFb)和最大呼气流速(PEFb)均低于爆炸前(P<0.05),80 m、200 m和240 m距离组大鼠呼吸频率明显高于对照组(P<0.05);40 m、80 m、120 m、160 m和200 m距离组大鼠肺组织LC3B相对表达量均高于对照组(P<0.05)。各距离组大鼠肺组织中Atg12和LC3BⅡ/Ⅰ相对表达水平高于对照组(P<0.05),40 m、80 m、120 m和160 m距离组大鼠肺组织中Beclin1相对表达量明显高于对照组(P<0.05),80 m、160 m和200 m距离组大鼠肺组织中P62相对表达量低于对照组(P<0.05),除240 m距离组外其余各距离组大鼠肺组织中Lamp2和Bcl-2相对表达水平低于对照组(P<0.05)。 结论: 瓦斯爆炸致ALI大鼠肺组织中细胞自噬作用增强,细胞自噬及其信号调控通路参与了瓦斯爆炸致大鼠ALI的病理生理过程,且损伤越重,自噬程度越为明显。.

Keywords: Acute lung injury; Autophagy; Gas explosion; Large roadway; Rats.

MeSH terms

  • Acute Lung Injury*
  • Animals
  • Autophagy
  • Explosions*
  • Lung
  • Rats
  • Rats, Sprague-Dawley