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[丝氨酸蛋白酶抑制剂作为急性肺损伤/急性呼吸窘迫综合征发病机制中的重要保护因素]

[Serpins as important protective factors in the pathogenesis of acute lung injury/acute respiratory distress syndrome].

作者信息

Zhang Jinquan, Xu Caiming, Zhang Guixin, Luo Yalan, Ge Peng, Chen Hailong

机构信息

Department of Abdominal Emergency Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China.

Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning, China. Corresponding author: Chen Hailong, Email:

出版信息

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Mar;33(3):368-372. doi: 10.3760/cma.j.cn121430-20200922-00644.

Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common respiratory disease in clinic, and with a pathological manifestation of pulmonary edema, decreased pulmonary compliance as well as pulmonary epithelial/endothelial cells injury. At present, it was suggested that systemic inflammatory response syndrome (SIRS) caused by various causes which play an important role in the occurrence and development of ALI/ARDS. Widely activated neutrophils can migrate to lung tissue and release plenty of proteases in the procedure of SIRS, including neutrophil serine proteases (NSPs), lysozyme, myeloperoxidase and collagenase, which can induce severe lung injury. Meanwhile, NSPs, such as neutrophil elastase (NE), cathepsin G (CG), proteinase 3 (PR3) and neutrophil serine proteinase 4 (NSP4), are important in the pathogenesis of ALI/ARDS. Therefore, Serpins may protect lung tissue by inhibiting NSPs. However, the specific mechanism of Serpins is not totally clear. In this article, we will discuss the mechanism of action of NSPs in the inflammatory response of ALI/ARDS, the structural overview of Serpins, the primary role of Serpins in ALI/ARDS, such as the inhibition of NSPs activity, other roles of Serpins in ALI/ARDS, such as the inhibition of inflammatory factor release, regulation of apoptosis and protection of vascular endothelial cells and pulmonary surfactant-associated glycoprotein D (SP-D), and the clinical application of exogenous Serpins in ALI/ARDS to explore the role of Serpins in the pathogenesis of ALI/ARDS. The aim is to provide new ideas and strategies for the clinical treatment of ALI/ARDS.

摘要

急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)是临床上常见的呼吸系统疾病,其病理表现为肺水肿、肺顺应性降低以及肺上皮/内皮细胞损伤。目前认为,由各种原因引起的全身炎症反应综合征(SIRS)在ALI/ARDS的发生发展中起重要作用。在SIRS过程中,广泛激活的中性粒细胞可迁移至肺组织并释放大量蛋白酶,包括中性粒细胞丝氨酸蛋白酶(NSPs)、溶菌酶、髓过氧化物酶和胶原酶,这些酶可导致严重的肺损伤。同时,NSPs,如中性粒细胞弹性蛋白酶(NE)、组织蛋白酶G(CG)、蛋白酶3(PR3)和中性粒细胞丝氨酸蛋白酶4(NSP4),在ALI/ARDS的发病机制中具有重要作用。因此,丝氨酸蛋白酶抑制剂(Serpins)可能通过抑制NSPs来保护肺组织。然而,Serpins的具体机制尚不完全清楚。在本文中,我们将讨论NSPs在ALI/ARDS炎症反应中的作用机制、Serpins的结构概述、Serpins在ALI/ARDS中的主要作用,如抑制NSPs活性,Serpins在ALI/ARDS中的其他作用,如抑制炎症因子释放、调节细胞凋亡以及保护血管内皮细胞和肺表面活性物质相关糖蛋白D(SP-D),以及外源性Serpins在ALI/ARDS中的临床应用,以探讨Serpins在ALI/ARDS发病机制中的作用。目的是为ALI/ARDS的临床治疗提供新的思路和策略。

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