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. H&E staining 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 NLRP3, ASC, and 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 MDA and ROS. The therapeutic effects of 8-Gingerol were associated with the regulation of MAPK and Nrf2/HO-1 pathways. These results support 8-Gingerol as a promising drug for the treatment of HS-induced ALI.
摘要：
急性肺损伤(ALI)是失血性休克(HS)后常见的并发症,这与HS诱导的炎症反应有关，氧化应激，和细胞凋亡。本研究旨在探讨8-姜酚的治疗效果，从生姜中提取的成分，大鼠HS后ALI。建立SD大鼠固定按压出血模型,其中HS大鼠在液体复苏前通过腹膜内注射15或30mg/kg的8-姜酚。H&E染色和TUNEL染色评价肺组织病理学改变和细胞凋亡,分别。使用定量逆转录PCR和蛋白质印迹来测量基因和蛋白质表达。通过ELISA试剂盒检测促炎细胞因子。髓过氧化物酶免疫荧光用于评估中性粒细胞浸润。8-姜辣素减轻肺水肿，肺泡壁厚度，HS年夜鼠肺组织细胞凋亡。关于炎症反应，8-姜辣素减弱肺组织中性粒细胞浸润，肺组织和支气管肺泡灌洗液中促炎细胞因子减少，并降低了NLRP3，ASC，并在肺组织中裂解半胱天冬酶1。此外,8-姜辣素改善了肺组织中的氧化应激,如通过增加的抗氧化指标(SOD和GSH)和减少的MDA和ROS的产生所证明的。8-姜酚的治疗作用与MAPK和Nrf2/HO-1通路的调节有关。这些结果支持8-姜酚作为治疗HS诱导的ALI的有希望的药物。
