BML-111, a lipoxin receptor agonist, protects against acute injury via regulating the renin angiotensin-aldosterone system
BML-111, a lipoxin receptor agonist, protects against acute injury via regulating the renin angiotensin-aldosterone system
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BML-111 是一种脂氧素受体激动剂，通过调节肾素血管紧张素-醛固酮系统防止急性损伤
DOI：
10.1016/j.prostaglandins.2018.11.001
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发表时间：
2019-02-01
影响因子：
2.9
通讯作者：
Zhou, Xiao-Yan
中科院分区：
文献类型：
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作者：
Chen, Qiong-Feng;Hao, Hua;Zhou, Xiao-Yan
背景：肾素-血管紧张素-醛固酮系统（RAAS）和脂氧素（LXs）在许多过程中具有相似的作用。我们以前报道过脂氧素受体激动剂BML-111通过调节RAAS抑制慢性损伤性肝纤维化，但LXs是否参与了BML-111介导的急性肝损伤保护作用尚不清楚。应用脂氧素受体激动剂BML-111来模拟LX的作用。分别用酶联免疫吸附法（ELISA）和活性测定试剂盒测定血管紧张素转换酶（ACE）和血管紧张素转换酶2（ACE 2）的含量和活性。结果：BML-111对LPS诱导的急性肺损伤和LPS/D-GalN诱导的急性肝损伤均有保护作用。BML-111抑制ACE活性，但增加ACE 2活性。BML-111可降低血管紧张素转换酶（ACE）、血管紧张素Ⅱ（AngII）和血管紧张素Ⅱ受体（AT 1 R）的表达水平，升高血管紧张素转换酶（ACE 2）、血管紧张素-（1-7）和血管紧张素转换酶（Mas）的表达水平。结论：BML-111通过调节RAAS对急性脑损伤具有保护作用。
Background: The renin angiotensin-aldosterone system (RAAS) and lipoxins (LXs) have similar roles in many processes. We previously reported that BML-111, a Lipoxin receptor agonist, inhibited chronic injury hepatic fibrosis by regulating RAAS, but whether LXs are involved in BML-111-mediated protection from acute injury is unclear still.Methods: We established models of acute liver/lung injury and confirmed them with histopathology and myeloperoxidase (MPO) measurements. BML-111, a lipoxin receptor agonist, was applied to mimic the effects of LXs. The contents and activities of angiotensin converting enzyme(ACE) and angiotensinconverting enzyme 2 (ACE2) were measured through ELISA and activity assay kits respectively. Angiotensin II (AngII), angiotensin-(1-7) (Ang-1-7), AngII type 1 receptor (AT1R), and Mas receptor were quantified with ELISA and Western blot.Results: Models of acute injury were established successfully and BML-111 protected LPS-induced acute lung injury and LPS/D-GalN-induced acute liver injury. BML-111 repressed the activity of ACE, but increased the activity of ACE2. BML-111 decreased the expression levels of ACE, AngII, and AT1R, meanwhile increased the levels of ACE2, Ang-(1-7), and Mas. Furthermore, BOC-2, an inhibitor of lipoxin receptor, reversed all the effects.Conclusion: BML-111 could protect against acute injury via regulation RAAS.