大黄中蒽醌类成分改善急性肺损伤的作用机制研究进展OA
Research progress on action mechanisms of Rheum palmatum anthraquinones in improving acute lung injury
急性肺损伤(ALI)及急性呼吸窘迫综合征(ARDS)是以炎症反应失控和肺泡-毛细血管屏障破坏为特征的一类严重呼吸系统疾病,该类疾病常由感染、脓毒症、创伤或吸入性损伤等多种因素诱发,病理过程涉及炎症级联反应、氧化应激失衡、免疫细胞异常活化以及肺微血管通透性增加等多个环节.其发病机制复杂、病死率高,但目前临床可用的治疗手段仍较为有限.因此,开发能够安全、有效缓解ALI 进程的治疗药物,已成为当前研究领域的热点.大黄作为传统中药,在清热解毒、通腑泄热和调控全身炎症反应方面具有悠久的应用基础,近年来其在 ALI 中的治疗作用逐渐受到关注.研究表明,大黄及其主要活性蒽醌类成分大黄素、大黄酚等可通过多靶点、多通路协同发挥保护作用,其机制主要包括抑制核因子 κB(NF-κB)、丝裂原活化蛋白激酶(MAPK)和 NOD 样受体蛋白 3(NLRP3)炎性小体等炎症信号通路,减轻氧化应激反应并激活核因子 E2 相关因子 2(Nrf2)介导的抗氧化防御体系,调控巨噬细胞等免疫细胞的程序性死亡方式,改善免疫代谢状态并调节巨噬细胞极化,调节肠道菌群和肠-肺轴等.此外,大黄还可通过保护肺泡-毛细血管屏障完整性、抑制中性粒细胞过度活化及中性粒细胞外陷阱(NETs)的过度形成,从而降低炎症放大效应和免疫性微血栓风险.该文总结了大黄在治疗 ALI 中的作用机制及研究进展,旨在揭示大黄蒽醌类成分通过系统调节网络干预 ALI 复杂病理进程的独特优势,为其创新药物研发与临床联合用药提供坚实的理论依据.
Acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are severe respiratory diseases characterized by uncontrolled inflammatory responses and disruption of the alveolar-capillary barrier.This type of disease is often triggered by multiple factors such as infection,sepsis,trauma,or inhalation injury,and the pathological process involves multiple sections including inflammatory cascade reactions,oxidative stress imbalance,abnormal activation of immune cells,and increased pulmonary microvascular permeability.Owing to their complex pathogenesis and high mortality,available clinical therapeutic approaches remain limited.Therefore,the development of safe and effective therapeutic agents to attenuate ALI has become a major focus of current research field.As a TCM,Rheum palmatum has a long history of use in clearing heat and toxins,purging the bowels,and regulating systemic inflammatory responses.In recent years,increasing attention has been paid to its therapeutic effect in ALI.Results show that R.palmatum and its major bioactive anthraquinones,such as emodin and rhein,exert protective effects through multi-target and multi-pathway mechanisms.These mechanisms mainly include inhibition of inflammatory signaling pathways such as nuclear factor-κB(NF-κB),mitogen-activated protein kinase(MAPK),and NOD-like receptor protein 3(NLRP3)inflammasome,attenuation of oxidative stress response,activation of the nuclear factor erythroid 2-related factor 2(Nrf2)-mediated antioxidant defense system,regulation of programmed death in immune cells including macrophages,improvement of immunometabolic status,modulation of macrophage polarization and the gut microbiota as well as the gut-lung axis,and so on.In addition,R.palmatum has been shown to preserve the integrity of the alveolar-capillary barrier and to suppress excessive neutrophil activation and the overformation of neutrophil extracellular traps(NETs),thereby reducing inflammation amplification effect and the risk of immune microthrombi.This paper summarized the action mechanisms and research progress of R.palmatum in the treatment of ALI,aiming to elucidate the unique advantages of R.palmatum anthraquinones in intervening in the complex pathological processes of ALI through systemic regulatory networks and to provide a solid theoretical basis for the research and development of innovative R.palmatum-based medicines and their clinical combination medication.
姚贵燕;朱达夫;谭波;王慧
三峡大学 生物与制药学院 天然产物研究与利用湖北省重点实验室,湖北 宜昌 443002同济大学 附属上海市肺科医院 呼吸与危重症医学科,上海 200433上海中医药大学 附属曙光医院 临床药代动力学实验室,上海 201203三峡大学 生物与制药学院 天然产物研究与利用湖北省重点实验室,湖北 宜昌 443002
大黄急性肺损伤作用机制蒽醌
Rheum palmatumacute lung injurymechanismanthraquinone
《中国中药杂志》 2026 (14)
3955-3963,9
国家自然科学基金面上项目(82574748)高等学校学科创新引智计划项目(D20015)天然产物研究与利用湖北省重点实验室(三峡大学)开放基金项目(2024NPRD10)
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