肾素-血管紧张素系统在急性呼吸窘迫综合征发病机制中的重要作用探讨

The Important Role of Renin-angiotensin System in the Pathogenesis of ARDS

急性呼吸窘迫综合征(ARDS)的特征是大量炎症、血管通透性增加和肺水肿。此病死亡率极高,即使患者存活,急性肺损伤也可能导致肺纤维化。肾素-血管紧张素系统(RAS)在疾病过程中起着重要作用。当机体受到损害时RAS相关分子的活性会发生动态变化。早期通过增加血管紧张素Ⅱ(AngⅡ)和去精氨酸缓激肽(DABK)的水平发挥防御作用。后期通过增强血管紧张素转换酶2(ACE2)活性减轻炎症,且适当增加的ACE2活性可能在预防免疫诱导的组织损伤和修复方面起决定性作用。ACE2已被认为是不同病原体的共同靶点,是SARS-CoV-2在内的一些冠状病毒的膜结合受体,与病毒与宿主细胞的融合、入侵过程有关。目前ARDS预后不良以及没有有效的治疗方法促使人们寻找新的治疗策略。在SARS-CoV-2大流行的背景下,考虑到体液失衡参与了ARDS的发病机制。靶向作用于RAS系统,减少病原体的细胞入侵可能是对抗新型冠状病毒感染的一种有前途的治疗策略。

Acute respiratory distress syndrome(ARDS)is characterized by massive inflammation,increased vascular permeability,and pulmonary edema.Mortality is extremely high,and acute lung injury can lead to pulmonary fibrosis even if the patient survives.The renin-angiotensin system(RAS)plays an important role in the disease process.The activity of RAS-related molecules changes dynamically when the body is damaged.It plays a defensive role in the early stage by increasing the levels of angiotensinⅡ(AngⅡ)and desarginine bradykinin(DABK).The later stage helps reduce inflammation by enhancing angiotensin-converting enzyme 2(ACE2)activity,and appropriately increased ACE2 activity may play a decisive role in preventing immune-induced tissue damage and repair.ACE2 has been considered as a common target of different pathogens,and it is the membrane-bound receptor of some coronaviruses including SARS-CoV-2,which is related to the fusion and invasion process of the virus and host cells.The current poor prognosis of ARDS and the lack of effective treatments have prompted the search for new therapeutic strategies.In the context of the SARS-CoV-2 pandemic,it is considered that fluid imbalances are involved in the pathogenesis of ARDS.Targeting the RAS system to reduce cellular invasion by pathogens may be a promising therapeutic strategy against COVID-19.