肾素-血管紧张素系统在ALI/ARDS中作用研究进展

Research progress on renin-angiotensin system in ALI/ARDS

急性肺损伤(ALI)是一种急性低氧性呼吸功能不全综合征;其容易发展为急性呼吸窘迫综合征(ARDS)。肾素-血管紧张素系统(RAS)被证实与ALI/ARDS发生发展密切相关。RAS的经典轴——血管紧张素转化酶(ACE)-血管紧张素(Ang)Ⅱ-AngⅡ1型受体(AT1R)轴通过诱导过度炎症反应、损伤肺泡屏障功能、触发凝血功能障碍等机制,诱导ALI/ARDS。RAS的ACE2-Ang(1-7)-Mas轴具有拮抗ACE-AngⅡ-AT1R轴的作用,通过抑制炎症反应、拮抗氧化应激、降低肺血管渗透性等机制,改善ALI/ARDS。ACE抑制剂、降低AngⅡ水平的药物、AT1R阻断剂、AT2R兴奋剂、重组ACE2、过表达ACE2的间充质干细胞、Ang1~7和脂氧素A4等,已被动物实验证实对ALI/ARDS有改善作用。这为防治ALI/ARDS、改善预后提供了新靶点。

Acute lung injury(ALI) is an acute hypoxic respiratory insufficiency syndrome. It tends to develop into acute respiratory distress syndrome(ARDS). Renin angiotensin system(RAS) has been proved to be closely related to the development of ALI/ARDS. The classic axis of RAS, angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang Ⅱtype 1 receptor(AT1R) axis, induces ALI/ARDS by inducing excessive inflammatory response, damaging alveolar barrier function, triggering coagulation dysfunction and other mechanisms. ACE2-Ang(1-7)-MAS axis of RAS can antagonize ACE-Ang Ⅱ-AT1R axis, and improve ALI/ARDS by inhibiting inflammatory response, antagonizing oxidative stress and reducing pulmonary vascular permeability. ACE inhibitors, drugs to reduce the level of Ang Ⅱ, AT1R blockers, AT2R stimulants, recombinant ACE2,mesenchymal stem cells with ACE2 overexpression, Ang1-7 and lipoxin A4 have been proved to improve ALI/ARDS in animal experiments. These results provide a new target for prevention and treatment of ALI/ARDS and improvement of prognosis.