基于Hippo信号通路探究自噬在脓毒症ARDS肺损伤中的作用机制

Based on the Hippo signaling pathway to explore the mechanism of autophagy in lung injury of acute respiratory distress syndrome induced by sepsis

各种致病因素所致全身炎症反应是急性呼吸窘迫综合征(ARDS)发生发展的关键阶段,目前临床上抑制炎症反应和对症支持是治疗ARDS的主要方法。肺泡上皮细胞自噬在ARDS炎症反应中具有重要的调节功能,细胞自噬本身是体内正常的免疫机制,是吞噬细胞借助溶酶体降解细胞内成分维持胞内稳态的代谢过程。目前研究表明,肺内外致病因素可通过引发炎症反应促使肺泡上皮细胞形成缺氧、饥饿、感染甚至凋亡的不利内环境,导致自噬功能紊乱,而过度的自噬激活可继续加重炎症反应。自噬相关蛋白Beclin1、微管相关蛋白1轻链3(LC3)、哺乳动物雷帕霉素靶蛋白(mTOR)、p62等是目前研究中常见的自噬标志物,在调控自噬过程及肺损伤发展中起着至关重要的作用,因此细胞自噬基因表达可作为脓毒症ARDS肺损伤的早期标志物及重要机制。Hippo通路来源于果蝇中的蛋白激酶Hippo,Hippo和自噬这两条保守的通路对于维持体内平衡至关重要。Hippo信号通路与细胞自噬的相互调控是目前学术界的热门话题,本文对相关文献进行回顾,探讨Hippo信号通路是否能够通过调控细胞自噬来缓解脓毒症ARDS的炎症反应,从而为ARDS治疗提供更进一步的研究方向。

The systemic inflammatory response caused by various pathogenic factors is a key stage in the development of acute respiratory distress syndrome(ARDS).At present,suppression of the inflammatory response and symptomatic support are main methods for the treatment of ARDS.Alveolar epithelial autophagy has an important role in the regulation of the inflammatory response in ARDS.Autophagy is a normal immune mechanism in the body,and it is a metabolic process by which phagocytes degrade intracellular components with the help of lysosomes to maintain intracellular homeostasis.Current studies have shown that pathogenic factors both inside and outside the lung can cause alveolar epithelial cells to form an unfavorable internal environment of hypoxia,starvation,infection,and even apoptosis by triggering inflammatory responses,leading to autophagy dysfunction.Excessive autophagy activation can continue to aggravate inflammatory responses.Autophagy related proteins such as Beclin1,microtubule-associated protein 1 light chain 3(LC3),mammalian target of rapamycin(mTOR),and p62 are common autophagic markers in current research,which play a crucial role in regulating the autophagic process and the development of lung injury.Therefore,the expression of cellular autophagy genes can be used as early markers and important mechanisms of lung injury in septic ARDS.The Hippo signaling pathway is derived from the protein kinase Hippo in Drosophila,and the Hippo and autophagy are two conserved pathways that are essential for the protection of homeostasis in vivo.The mutual regulation of Hippo signaling pathway and autophagy is currently a hot topic in the academic community.This paper reviews the relevant literature to explore whether the Hippo signaling pathway can regulate cellular autophagy to alleviate the inflammatory response in septic ARDS,so as to provide further research directions for the treatment of ARDS.