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Sulfasalazine ameliorates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress and nuclear factor-kappaB pathways
The International Journal of Biochemistry & Cell Biology ( IF 4 ) Pub Date : 2024-01-19 , DOI: 10.1016/j.biocel.2024.106530
Hai-peng Cheng , Xing-wen Bao , Yong-yu Luo , Yang-hang Li , Yan Zhou , Qing-zhong Hua , Yu-jia Qiu , Xin-yue Liang , Yan-hong Huang , Wei Liu , Si-yuan Tang , Dan-dan Feng , Chen Li , Zi-qiang Luo

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has a high mortality rate and incidence of complications. The pathophysiology of ALI/ARDS is still not fully understood. The lipopolysaccharide (LPS)-induced mouse model of ALI has been widely used to study human ALI/ARDS. Sulfasalazine (SASP) has antibacterial and anti-inflammatory effects and is used for treating inflammatory bowel and rheumatic diseases. However, the effect of SASP on LPS-induced ALI in mice has not yet been reported. Therefore, we aimed to investigate the effect of SASP on LPS-induced ALI in mice. Mice were intraperitoneally injected with SASP 2 h before or 4 h after LPS modeling. Pulmonary pathological damage was measured based on inflammatory factor expression (malondialdehyde and superoxide dismutase levels) in the lung tissue homogenate and alveolar lavage fluid. The production of inflammatory cytokines and occurrence of oxidative stress in the lungs induced by LPS were significantly mitigated after the prophylactic and long-term therapeutic administration of SASP, which ameliorated ALI caused by LPS. SASP reduced both the production of inflammatory cytokines and occurrence of oxidative stress in RAW264.7 cells, which respond to LPS. Moreover, its mechanism contributed to the suppression of NF-κB and nuclear translocation. In summary, SASP treatment ameliorates LPS-induced ALI by mediating anti-inflammatory and antioxidant effects, which may be attributed to the inhibition of NF-κB activation and promotion of antioxidant defenses. Thus, SASP may be a promising pharmacologic agent for ALI therapy.



中文翻译:

柳氮磺吡啶通过抑制氧化应激和核因子-κB 通路改善脂多糖诱导的急性肺损伤

急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)具有较高的死亡率和并发症发生率。ALI/ARDS 的病理生理学尚未完全了解。脂多糖(LPS)诱导的 ALI 小鼠模型已广泛用于研究人类 ALI/ARDS。柳氮磺吡啶 (SASP) 具有抗菌和抗炎作用,用于治疗炎症性肠病和风湿性疾病。然而,SASP 对 LPS 诱导的小鼠 ALI 的影响尚未见报道。因此,我们旨在研究 SASP 对 LPS 诱导的小鼠 ALI 的影响。 LPS造模前2小时或造模后4小时给小鼠腹腔注射SASP  。根据肺组织匀浆和肺泡灌洗液中的炎症因子表达(丙二醛和超氧化物歧化酶水平)来测量肺部病理损伤。预防性和长期治疗性给予SASP后,LPS引起的肺部炎症细胞因子的产生和氧化应激的发生明显减轻,从而改善了LPS引起的ALI。SASP 减少了对 LPS 做出反应的 RAW264.7 细胞中炎症细胞因子的产生和氧化应激的发生。此外,其机制有助于抑制 NF-κB 和核转位。总之,SASP 治疗通过介导抗炎和抗氧化作用改善 LPS 诱导的 ALI,这可能归因于抑制 NF-κB 激活和促进​​抗氧化防御。因此,SASP 可能是治疗 ALI 的有前途的药物。

更新日期:2024-01-19
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