BML-111 equilibrated ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis to protect hepatic fibrosis in rats

Publication date: Available online 16 August 2017
Source:Prostaglandins & Other Lipid Mediators
Author(s): Quandong Hu, Zhenzhen Hu, Qiongfeng Chen, Yonghong Huang, Zi Mao, Fangyun Xu, Xiaoyan Zhou
BackgroundIt 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.MethodsThe 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.ResultsThe 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 A4 receptor blocker, could reverse all these phenomena.ConclusionsEquilibrating ACE-AngII-AT1R axis and ACE2-Ang-(1-7)-Mas axis mediated the protective effect of BML-111 on hepatic fibrosis in rats.



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