Abstract
Acute lung injury (ALI) is a common complication after hemorrhagic shock (HS), which is associated with HS-induced inflammatory response, oxidative stress, and cell apoptosis. This study aimed to investigate the therapeutic efficacy of 8-Gingerol, a constituent extracted from ginger, on ALI after HS in rats. We established a fixed press hemorrhage model in SD rats, in which the HS rats were administered 15 or 30 mg/kg of 8-Gingerol by intraperitoneal injection before fluid resuscitation. Hematoxylin and eosin (H&E) and TUNEL staining were performed to evaluate histopathological changes and cell apoptosis in lung tissues, respectively. Quantitative reverse transcription PCR and western blot were used to measure gene and protein expression. Pro-inflammatory cytokines were detected by ELISA kits. Immunofluorescence of myeloperoxidase was used to evaluate neutrophil infiltration. 8-Gingerol reduced pulmonary edema, alveolar wall thickness, and cell apoptosis in lung tissues of HS rats. Regarding inflammatory responses, 8-Gingerol attenuated neutrophil infiltration in lung tissues, reduced pro-inflammatory cytokines in lung tissues and bronchoalveolar lavage fluid, and decreased the levels of NLR family, pyrin domain containing 3 (NLRP3), PYD and CARD domain containing (ASC), and Cleaved-Caspase 1 (Asp296), p20 (Cleaved Caspase 1) in lung tissues. Additionally, 8-Gingerol ameliorated oxidative stress in lung tissues as evidenced by increased antioxidant indicators (SOD and GSH) and decreased production of malondialdehyde (MDA) and reactive oxygen species (ROS). The therapeutic effects of 8-Gingerol were associated with the regulation of mitogen-activated protein kinase (MAPK) and Nrf2/HO-1 pathways. These results support 8-Gingerol as a promising drug for the treatment of HS-induced ALI.