PDF(Pubmed)
Abstract：
Inflammation is a natural protective process through which the immune system responds to injury, infection, or irritation. However, hyperinflammation or long-term inflammatory responses can cause various inflammatory diseases. Although idebenone was initially developed for the treatment of cognitive impairment and dementia, it is currently used to treat various diseases. However, its anti-inflammatory effects and regulatory functions in inflammatory diseases are yet to be elucidated. Therefore, this study aimed to investigate the anti-inflammatory effects of idebenone in cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation. Murine models of cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation were generated, followed by treatment with various concentrations of idebenone. Additionally, lipopolysaccharide-stimulated macrophages were treated with idebenone to elucidate its anti-inflammatory effects at the cellular level. Idebenone treatment significantly improved survival rate, protected against tissue damage, and decreased the expression of inflammatory enzymes and cytokines in mice models of sepsis and systemic inflammation. Additionally, idebenone treatment suppressed inflammatory responses in macrophages, inhibited the NF-κB signaling pathway, reduced reactive oxygen species and lipid peroxidation, and normalized the activities of antioxidant enzyme. Idebenone possesses potential therapeutic application as a novel anti-inflammatory agent in systemic inflammatory diseases and sepsis.
摘要：
炎症是免疫系统对损伤做出反应的自然保护过程，感染,或刺激。然而,炎症过度或长期炎症反应可引起各种炎症性疾病。尽管艾地苯醌最初被开发用于治疗认知障碍和痴呆，目前用于治疗各种疾病。然而,其在炎症性疾病中的抗炎作用和调节功能尚待阐明。因此,本研究旨在探讨艾地苯醌对盲肠结扎穿孔所致脓毒症及脂多糖所致全身炎症的抗炎作用。盲肠结扎穿刺诱导的脓毒症和脂多糖诱导的全身性炎症的小鼠模型，然后用不同浓度的艾地苯醌处理。此外,脂多糖刺激的巨噬细胞用艾地苯醌处理以阐明其在细胞水平的抗炎作用。艾地苯醌治疗显著提高生存率，防止组织损伤，降低脓毒症和全身性炎症小鼠模型中炎性酶和细胞因子的表达。此外,艾地苯醌治疗抑制了巨噬细胞的炎症反应，抑制NF-κB信号通路，减少活性氧和脂质过氧化，并使抗氧化酶的活性正常化。艾地苯醌作为一种新型抗炎药在全身性炎性疾病和脓毒症中具有潜在的治疗应用。
