关键词: 光气, 急性肺损伤, 咖啡酸苯乙酯, 氧化应激, 炎症

Abstract: OBJECTIVE：To investigate the mechanism of acute lung injury (ALI) induced by phosgene in rats and the protective effect of caffeic acid phenethyl ester (CAPE). METHODS：Thirty SD rats were randomly divided into a negative control group，a positive control group，a phosgene exposure group and a CAPE intervention group. The phosgene concentration was 10 mg/L and the dynamic exposure lasted for 3 min. After 6 h of exposure，pathological changes of lung tissue were determined，lung functions were detected，and lung coefficient was calculated. Total antioxidant capacity (T-AOC)，MDA concentration，MPO concentration，GSH concentration，CAT activity and SOD activity of lung tissues were detected using kits. Protein concentrations of bronchoalveolar lavage fluid (BALF) were detected by BCA method. Relative expression levels of TNF-α and IL-1β mRNA were detected by fluorescence quantitative PCR (qPCR). Concentrations of TNF-α and IL-1β in rat serum were detected by ELISA. Relative expression levels of DJ-1，Nrf2，Keap1 and SOD in rat lung tissue were detected by Western blot. RESULTS：Compared with the control group，the lung structure of rats exposed to 10 mg/L phosgene was significantly altered. The concentrations of MDA and MPO，activities of SOD，and protein concentrations of BALF were higher than those in the control group (P<0.01). The concentrations of GSH，activities of CAT and T-AOC were lower than those in the control group (P<0.01). The concentrations of TNF-α and IL-1β in the serum of the phosgene-exposed group were higher than those in the control group (P<0.01). The mRNA levels of TNF-α and IL-1β in lung tissues were higher than those in the control group (P<0.01). The expression levels of DJ-1 protein in the phosgene-exposed group were lower than that in the control group (P<0.05). Under the the CAPE intervention and compared with the phosgene exposure group lung injury was reduced，the concentrations of MDA and MPO，and the activities of SOD in lung tissue were lower (P<0.01)；the concentrations of GSH，the activities of CAT and T-AOC were higher (P<0.01)；the concentrations of TNF-α and IL-1β in the serum were lower (P<0.01)；the relative expression levels of TNF-α and IL-1β mRNA in lung tissues were lower (P<0.01)；the expression levels of DJ-1 protein in lung tissues were upregulated (P<0.05). CONCLUSION：The asphyxiating agent phosgene exposure caused lung injury in rats，and expression of DJ-1 molecule was decreased. CAPE intervention reduced lung injury，inhibited lung inflammation and oxidative stress，probably via antioxidant and anti-inflammatory mechanisms.

Key words: phosgene, acute lung injury, CAPE, oxidative stress, inflammation