m^(6)A修饰在脓毒症及其诱发的多器官功能障碍疾病中的作用及研究进展  

The role and research progress of m^(6)A modification in sepsisand its induced multi-organ dysfunction disease

作　　者：张璐璐 龚蕊 赵瑾怡 牟菲 尹艳萍 李旺廷 郑玲玲 唐于平 王婧雯 ZHANG Lu-lu;GONG Rui;ZHAO Jin-yi;MU Fei;YIN Yan-ping;LI Wang-ting;ZHENG Ling-ling;TANG Yu-ping;WANG Jing-wen(College of pharmacy,Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712046,China;Dept of Pharmacy,Xijing Hospital,the Fourth Military Medical University,Xian 710032,China;The College of Life Sciences,Northwest University,Xian 710069,China)

机构地区：[1]陕西中医药大学药学院,陕西咸阳712046 [2]空军军医大学西京医院药剂科,陕西西安710032 [3]西北大学生命科学学院,陕西西安710069

出　　处：《中国药理学通报》2025年第3期421-427,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81774190)。

摘　　要：脓毒症是一种由于宿主对感染的反应失调而导致的危及生命的器官功能障碍性疾病。其具有复杂的病理生理学改变,严重时可迅速发展为脓毒性休克和多器官功能障碍或多器官功能衰竭。目前,脓毒症及其诱发的多种器官功能障碍病理机制复杂、影响因素众多,至今仍缺乏特异性的有效治疗策略。RNA修饰-N^(6)-甲基化腺嘌呤(N^(6)-methyladenosine,m^(6)A)是存在于真核生物RNAs上最常见的转录后修饰之一,通过影响RNAs代谢参与调节包括脓毒症在内的多种炎症性疾病发生与发展,甚至涉及脓毒症诱发的多器官功能障碍,包括心功能障碍、急性肺损伤(acute lung injury,ALI)和急性肾损伤(acute kidney injury,AKI)等。因此,该文将讨论m^(6)A修饰对免疫细胞功能的影响,以及其通过调节炎症信号、细胞焦亡、线粒体损伤和铁死亡等在脓毒症及其诱发的多器官功能障碍疾病中发挥的重要作用。这将为脓毒症及其诱发的多器官功能障碍性疾病的临床防治提供新的治疗靶点与策略。Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has complex pathophysiological changes,and in severe cases,it can rapidly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the influencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N^(6)-methyladenosine(m^(6)A)is one of the most common post-transcriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will discuss the effect of m^(6)A modification on the function of immune cells,and its important role in sepsis and its induced multiple organ dysfunction diseases by regulating inflammatory signals,pyroptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunction diseases.

关 键 词：m^(6)A修饰 脓毒症 免疫抑制 炎症反应 转录后调控 多器官功能障碍 

分 类 号：R342.2[医药卫生—基础医学] R364.5R365R631