BML-111 equilibrated ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis to protect hepatic fibrosis in rats
BML-111 equilibrated ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis to protect hepatic fibrosis in rats
复制标题
BML-111平衡ACE-AngII-AT1R和ACE2-Ang-(1-7)-Mas轴以保护大鼠肝纤维化
DOI：
10.1016/j.prostaglandins.2017.08.008
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发表时间：
2017-07-01
影响因子：
2.9
通讯作者：
Zhou, Xiaoyan
中科院分区：
文献类型：
--
作者：
Hu, Quandong;Hu, Zhenzhen;Zhou, Xiaoyan
背景资料：近年来研究发现脂氧素（Lipoxins，LXs）对肝纤维化具有保护作用，而肾素-血管紧张素-醛固酮系统（Renin-Angiotensin-Aldosterone System，RAAS）在肝纤维化中起着重要的双向作用。本文采用四氯化碳（CCL_4）诱导的大鼠肝纤维化模型，观察肝动脉粥样硬化（RAAS）与LXs的关系，并进一步探讨LXs抗肝纤维化的可能机制。采用试剂盒和酶联免疫吸附法检测血管紧张素转换酶（ACE）和血管紧张素转换酶2（ACE 2）的活性和含量。采用真实的PCR、ELISA和Western blot检测血管紧张素II（ArgII）、血管紧张素II 1型受体（AT 1 R）、血管紧张素1-7（Ang-1-7）和Mas的表达水平。BML-111能显著减轻CCL 4诱导的肝纤维化，包括减轻炎症损伤，减少细胞外基质沉积，改善肝功能。BML-111不仅能明显降低CCL 4诱导的ACE活性，还能降低CCL 4诱导的ACE、AngII和AT 1 R的表达水平。BML-111可显著增加ACE 2活性，增加ACE 2、Ang-（1-7）和Mas的表达。结论：BML-111通过平衡ACE-Ang Ⅱ-AT 1 R轴和ACE 2-Ang-（1-7）-Mas轴介导对大鼠肝纤维化的保护作用。
Background: It was recently reported Lipoxins (LXs) had protective effects on fibrous diseases, and renin-angiotensin-aldosterone system (RAAS) had played vital and bidirectional roles in hepatic fibrosis. In this paper, a hepatic fibrosis model, induced by carbon tetrachloride (CCL4) in rats, was used to observe the relations between RAAS and LXs, as well as to further explore the alternative anti-fibrosis mechanisms of LXs.Methods: The model was evaluated by morphological observations and biochemical assays. The activities and contents of angiotensin converting enzyme (ACE) and angiotensin converting enzyme 2 (ACE2) were examined through assay kits and ELISA. The expression levels of angiotensinII (ArgII), Angiotensin II type 1 receptor (AT1R), angiotensin-(1-7) (Ang-1-7), and Mas were all measured using real time PCR, ELISA, and Western blot.Results: The model was established successfully and BML-111 significantly ameliorated CCL4-induced hepatic fibrosis, including reduction inflammation injury, decrease extracellular matrix deposition, and improvement hepatic functions. Furthermore, BML-111 could obviously decrease not only the activities of ACE but also the expression levels of ACE, AngII and AT1R, which were induced by CCL4. On the other hand, BML-111 could markedly increase the activities of ACE2, besides the expression levels of ACE2, Ang-(1-7) and Mas. More importantly, BOC-2, a lipoxin A(4) receptor blocker, could reverse all these phenomena.Conclusions: Equilibrating ACE-AngII-AT1R axis and ACE2-Ang-(1-7)-Mas axis mediated the protective effect of BML-111 on hepatic fibrosis in rats.