摘要
脓毒症晚期发生持续性炎症反应、免疫抑制和分解代谢综合征(PICS),而T淋巴细胞功能障碍是PICS的重要特征。T淋巴细胞的营养代谢状态严重影响其免疫功能。脓毒症时各种信号分子包括营养素,通过磷脂酰肌醇-3激酶(PI3K)-丝氨酸/苏氨酸激酶(Akt)-哺乳动物雷帕霉素靶蛋白(mTOR)信号通路促进T淋巴细胞发生代谢重编程,从而改变其免疫表型。胰高血糖素样肽-1(GLP-1)是一种调节物质和能量代谢的肠促胰素,具有降糖、免疫抑制和抗炎的作用,脓毒症时其水平急剧升高,并与危重患者的病情和预后密切相关。GLP-1受体(GLP-1R)激动剂可阻断T淋巴细胞的糖酵解,抑制葡萄糖转运蛋白mRNA的表达,从而抑制T淋巴细胞增殖。因此,脓毒症时内源性GLP-1水平升高可能代表机体能量代谢向有氧糖酵解转换,反映的是PICS的一种病理状态。本文阐述GLP-1对脓毒症T淋巴细胞免疫功能和代谢重编程的调控作用,以为通过GLP-1R防治脓毒症T淋巴细胞功能障碍提供策略参考。
Persistent inflammation,immuno-suppression and catabolism syndrome(PICS)occurs at the later stage of sepsis,characterized by T cell dysfunction with severe poor outcome.Recent studies found that T cell function be largely affected by its metabolic status.In sepsis,a variety of signaling molecules,including the nutrients,could trigger T cell to undergo metabolic reprogramming that from oxidative phosphorylation to aerobic glycolysis via phosphatidylinositol 3-kinase(PI3K)-serine/threonine kinases(Akt)-mammalian target of rapamycin(mTOR)pathway,leading to severe alterations of its immune phenotype.Glucagonlike peptide-1(GLP-1)is a kind of incretin hormone that could regulate nutrients and energy metabolism in the body.It can reduce blood glucose level,suppress the immune and inflammatory responses.Plasma GLP-1 levels were rapidly elevated in sepsis and correlated closely with the outcome in critical care.GLP-1 receptor(GLP-1R)agonist could block the glycolysis of T cells,reduce glucose transporter type 1 mRNA expression,and inhibit T cell proliferation.Therefore,the elevated GLP-1 level may represent the metabolic switch toward"aerobic glycolysis",reflecting the pathological status of PICS.Here,the review elucidates the regulation of GLP-1 on the immune function and metabolic reprogramming of T cells and provides strategies for the prevention and treatment of T cell immune dysfunction in sepsis via GLP-1 receptor.
作者
刘红升
张庆红
Liu Hong-Sheng;Zhang Qing-Hong(Department of Emergency,the Fourth Medical Center of Chinese PLA General Hospital,Beijing 100048,China;Trauma Repair and Tissue Regeneration Center,Department of Medical Innovation Study,Chinese PLA General Hospital,Beijing 100853,China)
出处
《解放军医学杂志》
北大核心
2025年第4期483-489,共7页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金面上项目(82172125)。
作者简介
刘红升,博士研究生,副主任医师,主要从事脓毒症的肠道黏膜屏障损伤机制研究;通信作者:张庆红,E-mail:z_qinghong@aliyun.com。
