Abstract Sepsis-induced lung injury was the most common cause of death in patients. Topiroxostat, a novel xanthine oxidoreductase inhibitors, possessed obvious organ protectives effects. Xanthine oxidase played a vital role in acute lung injury. The study aimed to investigate the roles of Topiroxostat in sepsis-induced lung injury. The sepsis rats were established using cecum ligation and perforation. The lung damage induced by sepsis was evaluated by Hematoxylin and Eosin staining and lung tissue wet to dry ratio. The oxidative stress was detected by measurement of reactive oxygen species, malondialdehyde, myeloperoxidase and superoxide dismutase (SOD). The pro-inflammatory mediators, tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and monocyte chemotactic protein 1, were measured by Enzyme-Linked Immunosorbent Assay. The cell apoptosis in lung was detected by TUNNEL staining and western blot analysis of apoptosis-related proteins including pro-apoptosis proteins, Bax, cleaved caspase9, cleaved caspase3 and anti-apoptosis protein Bcl2. The results showed that Topiroxostat significantly reduced lung damage, along with decreased oxidative stress, inflammation response and apoptosis in sepsis rats. Topiroxostat exerted markedly protective effects in sepsis-induced lung injury and could be an antioxidant in treating sepsis-induced lung injury.

中文翻译：

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Topiroxostat 改善败血症引起的肺损伤中的氧化应激和炎症

摘要 脓毒症引起的肺损伤是患者最常见的死亡原因。Topiroxostat是一种新型黄嘌呤氧化还原酶抑制剂，具有明显的器官保护作用。黄嘌呤氧化酶在急性肺损伤中起重要作用。该研究旨在调查 Topiroxostat 在败血症诱导的肺损伤中的作用。采用盲肠结扎穿孔法建立败血症大鼠。通过苏木精和伊红染色和肺组织湿干比评估败血症引起的肺损伤。通过测量活性氧、丙二醛、髓过氧化物酶和超氧化物歧化酶 (SOD) 来检测氧化应激。通过酶联免疫吸附测定法测量促炎介质、肿瘤坏死因子-α、白细胞介素 (IL)-1β、IL-6 和单核细胞趋化蛋白 1。肺细胞凋亡通过TUNNEL染色和凋亡相关蛋白Western blot分析检测，包括促凋亡蛋白、Bax、cleaved caspase9、cleaved caspase3和抗凋亡蛋白Bcl2。结果表明，Topiroxostat 显着减少了败血症大鼠的肺损伤，同时降低了氧化应激、炎症反应和细胞凋亡。Topiroxostat 在脓毒症引起的肺损伤中发挥显着的保护作用，并且可能是治疗脓毒症引起的肺损伤的抗氧化剂。脓毒症大鼠的炎症反应和细胞凋亡。Topiroxostat 在脓毒症引起的肺损伤中发挥显着的保护作用，并且可能是治疗脓毒症引起的肺损伤的抗氧化剂。脓毒症大鼠的炎症反应和细胞凋亡。Topiroxostat 在脓毒症引起的肺损伤中发挥显着的保护作用，并且可能是治疗脓毒症引起的肺损伤的抗氧化剂。