BML-111平衡了ACE-血管紧张素II-AT1R轴和ACE2-血管紧张素-(1-7)-Mas轴，以保护大鼠的肝纤维化。
BML-111 equilibrated ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis to protect hepatic fibrosis in rats.
作者信息
Hu Quandong, Hu Zhenzhen, Chen Qiongfeng, Huang Yonghong, Mao Zi, Xu Fangyun, Zhou Xiaoyan
机构信息
Department of Pathophysiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, PR China.
Department of Pathophysiology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, PR China; Jiangxi Province Key Laboratory of Tumor pathogenesis and Molecular Pathology, Nanchang, Jiangxi 330006, PR China.
出版信息
Prostaglandins Other Lipid Mediat. 2017 Jul;131:75-82. doi: 10.1016/j.prostaglandins.2017.08.008. Epub 2017 Aug 16.
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 (CCL) 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 (AngII), 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 CCL-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 CCL. 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 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.
背景
最近有报道称脂氧素（LXs）对纤维化疾病具有保护作用，且肾素 - 血管紧张素 - 醛固酮系统（RAAS）在肝纤维化中发挥着重要的双向作用。本文采用四氯化碳（CCL）诱导大鼠建立肝纤维化模型，以观察RAAS与LXs之间的关系，并进一步探讨LXs的抗纤维化作用机制。
方法
通过形态学观察和生化检测对模型进行评估。使用试剂盒和酶联免疫吸附测定法检测血管紧张素转换酶（ACE）和血管紧张素转换酶2（ACE2）的活性及含量。采用实时荧光定量聚合酶链反应、酶联免疫吸附测定法和蛋白质免疫印迹法检测血管紧张素II（AngII）、血管紧张素II 1型受体（AT1R）、血管紧张素 - （1 - 7）（Ang - 1 - 7）和Mas的表达水平。
结果
成功建立模型，BML - 111显著改善了CCL诱导的肝纤维化，包括减轻炎症损伤、减少细胞外基质沉积以及改善肝功能。此外，BML - 111不仅能明显降低CCL诱导的ACE活性，还能降低ACE、AngII和AT1R的表达水平。另一方面，BML - 111除了能显著提高ACE2、Ang - （1 - 7）和Mas的表达水平外，还能明显提高ACE2的活性。更重要的是，脂氧素A受体阻滞剂BOC - 2可逆转所有这些现象。
结论
平衡ACE - AngII - AT1R轴和ACE2 - Ang - （1 - 7） - Mas轴介导了BML - 111对大鼠肝纤维化的保护作用。
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