Intervention effect of lipoxygen receptor agonist BML-111 on acute liver injury in rats and its mechanism

Abstract

Objective: To investigate the effect and mechanism of lipoxygen on acute liver injury. Methods: Twenty-four SD rats were randomly divided into 4 groups (n=6): normal control group: subcutaneous injection of olive oil at a dose of 1.8 ml/kg; model group: subcutaneous injection of 40% carbon tetrachloride(CCL4)oil (olive oil as a solvent) at a dose of 3 ml/kg; BML-111 treatment group: Lipoxin receptor agonist BML-111 was injected subcutaneously at a dose of 1 mg/kg, and treated in the same model group after 30 minutes; BOC-2 blocker group: Lipoxin receptor blocker BOC-2 was injected subcutaneously at a dose of 50 μg/kg. After 30 minutes, the treatment was the same as BML-111 group. HE staining was used to observe the pathological changes of liver tissues to judge the liver injury. Serological detection was used to determine the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST); The myeloperoxidase (MPO) activity in rat liver tissue was detected by kit method; the contents of of angiotensin converting enzyme (ACE) , Angiotensin converting enzyme 2 (ACE2), angiotensin II (AngII) and angiotensin 1-7 (Ang- (1-7)) were detected by ELISA. Western Blot was used to detect the protein contents of Ang II and Ang- (1-7) in liver tissue. Results: The treatment group had less liver damage than the model group and the blocker group; BML-111 decreased the levels of ACE and AngII in serum of rats with CCL4 injury (P＜0.01) and increased the levels of ACE2 and Ang- (1 in serum -7) content (P＜0.01). BML-111 increased the content of Ang- (1-7) in liver tissue and decreased the content of AngII in CCL4 injured rat tissue. Conclusion: The results showed that the intervention effect and mechanism of lipoxygen receptor agonist BML-111 on acute liver injury in rats may be related to the regulation of AngII and Ang-(1-7).