黄芪甲苷调控Nrf2/Keap1信号通路抗脓毒症急性肺损伤效应机制的研究OA
Study on the mechanism of the anti-sepsis acute lung injury effect of Astragaloside Ⅳ by modulating Nrf2/Keap1 signaling pathway
探讨黄芪甲苷(astragaloside Ⅳ,AS-Ⅳ)改善脓毒症急性肺损伤的效应机制.采用盲肠结扎穿刺术(CLP)构建脓毒症急性肺损伤模型,药物干预后,检测氧化应激指标和Nrf2/Keap1信号通路相关蛋白和mRNA表达.结果显示AS-Ⅳ药物干预提高脓毒症小鼠的生存率,改善肺组织病理损伤程度,降低炎症因子水平,降低活性氧(ROS)、丙二醛(MDA)、髓过氧化物酶(MPO)氧化应激指标,而升高SOD活性.AS-Ⅳ干预显著升高核因子E2相关因子2(Nrf2)、血红素氧合酶1(HO-1)蛋白和mRNA表达.Nrf2抑制剂ML385可显著逆转AS-Ⅳ对小鼠生存率的改善及肺组织病理损伤的减轻作用,明显抑制AS-Ⅳ诱导的SOD活性升高.ML385干预减少AS-Ⅳ促Nrf2和HO-1蛋白表达和mRNA水平升高.AS-Ⅳ显著改善脓毒症所致的急性肺损伤,抑制氧化应激反应,其作用机制可能与激活Nrf2/Keap1信号通路有关.
This study aimed to investigate the mechanism of astragaloside Ⅳ(AS-Ⅳ)in improving sepsis-induced acute lung injury.A model of sepsis-induced acute lung injury was established by cecal ligation and puncture(CLP).After drug intervention,the oxidative stress index and Nrf2/Keap1 signaling pathway-related protein and mRNA expression were detected.The results showed that AS-Ⅳ drug intervention improved the survival rate of septic mice,improved the degree of pathological injury of lung tissue,reduced the level of inflammatory factors,reduced ROS,MDA,and MPO oxidative stress indicators,and increased SOD activity.AS-Ⅳ intervention significantly increased the protein and mRNA expressions of Nrf2 and HO-1.The Nrf2 inhibitor ML385 could significantly reverse the improvement in survival rate and the alleviation of lung pathological injury induced by AS-Ⅳ in mice,and significantly inhibit the increase in SOD activity induced by AS-Ⅳ.ML385 intervention reduced AS-Ⅳ-induced Nrf2 and HO-1 protein expression and mRNA levels.AS-Ⅳ can significantly improve acute lung injury induced by sepsis and inhibit oxidative stress response.Its mechanism may be related to the activation of the Nrf2/Keap1 signaling pathway.
莫庆艳;王敏;巨鸣谦;张春菲;张浩洪;刘帅;黄茂葵;邹楠婷;李晓红;万春平
云南省第一人民医院云南省呼吸系统疾病临床医学研究中心,云南 昆明 650500||云南中医药大学中药学院,云南 昆明 650500云南省第一人民医院云南省呼吸系统疾病临床医学研究中心,云南 昆明 650500云南中医药大学基础医学院,云南 昆明 650500云南中医药大学中药学院,云南 昆明 650500云南中医药大学中药学院,云南 昆明 650500云南中医药大学中药学院,云南 昆明 650500云南中医药大学基础医学院,云南 昆明 650500云南中医药大学中药学院,云南 昆明 650500云南中医药大学第一临床医学院,云南 昆明 650500云南省中医医院中心实验室,云南 昆明 650500
医药卫生
黄芪甲苷脓毒症急性肺损伤Nrf2/Keap1信号通路
astragaloside Ⅳsepsisacute lung injuryNrf2/Keap1 signaling pathway
《云南民族大学学报（自然科学版）》 2026 (3)
300-308,9
国家自然科学基金(81960745)云南省呼吸系统疾病临床医学研究中心开放课题(202102AA100057).
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