氧化应激致自噬在光气诱导的急性肺损伤中的作用

doi:10.3969/j.issn.1004-616x.2023.05.001

Abstract

Abstract: OBJECTIVE: To explore changes of oxidation levels in lung tissues among the phosgeneexposedrats,and to investigate if oxidative stress would regulate autophagy to alleviate phosgene-induced acute lung injury (ALI) in rats. METHODS: Fifty rats were divided into five groups:control and treatment groups with phosgene treatment for 30 minutes and evaluated6,12,24 and 48 h later. The rats in the control group inhaled air through their noses, and the rats in the phosgene exposure group inhaled 41 mg/m³ of phosgene through their noses. After detecting relevant indicators,the 12 h post-exposure group was selected as the animal model for this study (hereinafter referred to as the phosgene group). Another 40 rats were divided into a control group (intraperitoneal injection of 0.9% normal saline),a phosgene group (41 mg/m³ of phosgene exposure for 30 min),and an RPM treatment group (intraperitoneal injection of 5 mg/kg of RPM after exposure) and the RPM control group (intraperitoneal injection of 5 mg/kg of RPM). Another 40 rats were divided into the control group (intraperitoneal injection of 0.9% normal saline), the phosgene group (41 mg/m³ of phosgene exposure for 30 min),and the NAC treatment group (the intraperitoneal injection of 200 mg/kg of NAC after exposure) and NAC control group (intraperitoneal injection of 200 mg/kg of NAC). These rats were observed for pathological changes in lung tissues; lung functions, lung moisture mass, lung coefficient, total protein concentration of bronchoalveolar lavage fluid (BALF), rat lung tissue ROS levels, lung tissue lipid peroxidation levels, anti-Oxidase (SOD, CAT) activity and GSH content, and redox and autophagy-related molecule mRNA and protein expression levels. RESULTS: Compared with the control group,histopathological observation at different time points after phosgene exposure showed alveolar fusion and increased inflammatory cells. Lung function decreased significantly (P<0.05 or 0.01). The lung moisture mass, lung coefficient and BALF total protein concentration were significantly increased (P<0.05 or 0.01). The levels of ROS and lipid peroxidation in lung tissues of rats were increased (P<0.01). The activity and expression levels of a series of antioxidant enzymes were changed (P<0.05 or 0.01),and the changes were most significant at 12 h after exposure. Compared with the control group, expression levels of autophagy-associated proteins, Beclin-1 and LC3II/LC3I, decreased in phosgene group,while the expression levels of P62 increased (P<0.05 or 0.01). Compared with phosgene group, the autophagy levels in RPM and NAC groups were up-regulated (P<0.05) and the phosgene induced ALI was alleviated. At the same time, the ROS level of lung tissue was decreased in the NAC treatment group. CONCLUSION: Oxidation levels of lung tissues increased at different time points after phosgene exposure. At the same time, oxidative stress regulated the level of autophagy. Administration of NAC alleviated oxidative stress,thereby upregulated autophagy levels and improved phosgene-induced ALI in rats.

Key words: phosgene, acute lung injury, oxidative stress, autophagy

CLC Number:

GUO Xiaojie, LIU Penghui, LONG Zi, LI Jiawei, TU Yongmei, LI Wenli, LIU Qiling. Induction of autophagy by oxidative stress in phosgene-induced acute lung injury[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(5): 325-333,340.

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Induction of autophagy by oxidative stress in phosgene-induced acute lung injury

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