PI3K-Akt-mTOR通路在慢阻肺发病机制中的研究进展

唐艺玲　张培蓓　叶贤伟

[关键词] PI3K-Akt-mTOR;慢性阻塞性肺疾病（慢阻肺）;自噬;基因治疗

[中图分类号] R856.3          [文献标识码] A          [文章编号] 1673-9701（2021）18-0178-06

Research progress of PI3K-Akt-mTOR pathway in the pathogenesis of chronic obstructive pulmonary disease

TANG Yiling1   ZHANG Peibei2，3   YE Xianwei1， 3

1.Zunyi Medical University，Zunyi 563000，China;2.Department of Respiratory and Critical Care Medicine，Guizhou Provincial People's Hospital， Guiyang 550000， China; 3.Key Laboratory of Pulmonary Immune Diseases， National Health Commission， Guiyang   550000， China

[Abstract] Chronic obstructive pulmonary disease （abbreviated as COPD）， which is an inflammatory disease of the airway in the respiratory mechanism of the human body， has a certain commonness， and its morbidity and fatality rate are both high. It is an important global public health issue. Through related investigations， it is found that the phosphatidylinositol 3-kinase/protein kinase B/target of rapamycin （P13K-Akt-mTOR） signaling pathway is involved in many aspects of the cell， such as proliferation， apoptosis， and autophagy， which is a classic signaling pathway in cell tissue and affects the prognosis and outcome of various diseases in different systems. Experts and scholars at home and abroad have made a certain degree of progress in the study of the PI3K-Akt-mTOR signal transduction pathway in the process of tumor cell proliferation， autophagy， and apoptosis after a large number of studies. However， there is still little involvement in the research field of the relationship between PI3K-Akt-mTOR signaling pathway and chronic obstructive pulmonary disease. This article reviews the research progress of the relationship between PI3K-Akt-mTOR pathway and COPD in recent years.

[Key words] PI3K-Akt-mTOR; Chronic obstructive pulmonary disease （COPD）; Autophagy; Gene therapy

慢性阻塞性肺疾病（慢阻肺）是一種具有气流受限特征的常见慢性呼吸系统疾病，当下有关慢阻肺病症的发病机制理论来讲，包含吸烟行为和人体慢性气道及人体肺部炎症的构成、蛋白酶/抗蛋白酶失衡、氧化剂及抗氧化剂的平衡失调等，此类理论大体着重于人体气道的上皮及炎症两大组织细胞在慢阻肺病症发生、发展的相关作用，但慢阻肺的致病机制非常复杂，如今尚未完全阐明，现多认为慢阻肺其特征是不可逆的慢性气流受限所引起的肺弹性组织破坏和（或）炎症黏性分泌物导致小气道管腔狭窄，且炎症免疫细胞的相互作用导致组织的破坏及弹性蛋白、胶原蛋白的改变，最终出现气道重塑[1]。细胞自噬是一个进化保守的分解代谢途径，细胞自噬增加可能会导致上皮细胞死亡，但自噬储备不足亦可导致慢阻肺患者支气管上皮细胞的衰老[2]。然而，过度的自噬会诱导过度的细胞损伤，导致程序性细胞死亡。研究表明磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶（mTOR）信号通路在自噬中起着关键的调节作用[3]。目前有实验证明，乳腺癌[4]、小细胞肺癌、胶质母细胞瘤[5]等疾病均与PI3K-Akt-mTOR信号通路相关。但在PI3K-Akt-mTOR信号传导通路与慢阻肺相互关系的研究涉足较少。本文就PI3K-AKT-mTOR信号通路对于慢阻肺的发生之间关系予以相应论证叙述。……