Xiao Hu1, Haitao Shen1, Yu Wang1, Lichun Zhang1, Min Zhao2. 1. Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China. 2. Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: zhaom@sj-hospital.org.
Abstract
AIMS: In the present study, we aimed to evaluate the role of aspirin-triggered resolvin D1 (AT-RvD1) in paraquat (PQ)-induced acute lung injury (ALI) in mice. MAIN METHODS: We used C57BL/6J mice as experimental subjects to establish mouse models of ALI via intraperitoneal (IP) injection of PQ (28 mg/kg). The mice were then administered AT-RvD1 (10 or 100 ng) via the tail vein 2 h after exposure to PQ and were sacrificed at 72 h post exposure to harvest bronchoalveolar lavage fluid (BALF), blood and lung tissue samples. The samples were used to evaluate the histopathological changes, inflammation reaction and oxidative stress in the lung tissues. KEY FINDINGS: Compared with those of the PQ group, the administration of AT-RvD1 significantly (1) alleviated the histopathological changes in the lung tissues; (2) reduced the lung W/D weight ratio and the total protein content in the BALF; (3) activated nuclear factor erythroid-2 related factor 2 (Nrf2) and up-regulated the expression of its downstream genes (NADPH: quinone oxidoreductase-1, NQO1 and heme oxygenase-1, HO-1); (4) reduced the malondialdehyde(MDA) level in the lung tissues; (5) reduced the total cell, neutrophil, and macrophage counts in the BALF; (6) reduced the myeloperoxidase (MPO) activity in the lung tissues; (7) reduced the percent of Ly-6G+ CD41+ cells in the peripheral blood; (8) inhibited the activation of nuclear factor-κB (NF-κB) and the expression of P-selectin; and (9) reduced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in the BALF. SIGNIFICANCE: Administration of AT-RvD1 can effectively inhibit PQ-induced oxidative stress injury, inflammatory responses, and pulmonary edema, thereby alleviating PQ-induced ALI.
AIMS: In the present study, we aimed to evaluate the role of aspirin-triggered resolvin D1 (AT-RvD1) in paraquat (PQ)-induced acute lung injury (ALI) in mice. MAIN METHODS: We used C57BL/6J mice as experimental subjects to establish mouse models of ALI via intraperitoneal (IP) injection of PQ (28 mg/kg). The mice were then administered AT-RvD1 (10 or 100 ng) via the tail vein 2 h after exposure to PQ and were sacrificed at 72 h post exposure to harvest bronchoalveolar lavage fluid (BALF), blood and lung tissue samples. The samples were used to evaluate the histopathological changes, inflammation reaction and oxidative stress in the lung tissues. KEY FINDINGS: Compared with those of the PQ group, the administration of AT-RvD1 significantly (1) alleviated the histopathological changes in the lung tissues; (2) reduced the lung W/D weight ratio and the total protein content in the BALF; (3) activated nuclear factor erythroid-2 related factor 2 (Nrf2) and up-regulated the expression of its downstream genes (NADPH: quinone oxidoreductase-1, NQO1 and heme oxygenase-1, HO-1); (4) reduced the malondialdehyde(MDA) level in the lung tissues; (5) reduced the total cell, neutrophil, and macrophage counts in the BALF; (6) reduced the myeloperoxidase (MPO) activity in the lung tissues; (7) reduced the percent of Ly-6G+ CD41+ cells in the peripheral blood; (8) inhibited the activation of nuclear factor-κB (NF-κB) and the expression of P-selectin; and (9) reduced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in the BALF. SIGNIFICANCE: Administration of AT-RvD1 can effectively inhibit PQ-induced oxidative stress injury, inflammatory responses, and pulmonary edema, thereby alleviating PQ-induced ALI.