脂氧素受体激动剂BML-111对大鼠急性肝损伤的干预作用及其机制

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

目的:探索脂氧素对急性肝损伤的作用及机制。方法:SD大鼠24只随机分为4组(n=6):正常对照组:皮下注射橄榄油,剂量1.8 ml/kg。模型组:皮下注射40%四氯化碳(CCL4)油剂(橄榄油为溶剂),剂量3 ml/kg。BML-111治疗组:皮下注射Lipoxin受体激动剂BML-111,剂量1 mg/kg,30 min后处理同模型组。BOC-2阻断剂组:皮下注射Lipoxin受体阻断剂BOC-2,剂量50μg/kg,30 min后处理同BML-111组。HE染色观察肝组织病理学变化,判断肝损伤情况。血清学检测血清谷丙转氨酶(ALT)及谷草转氨酶(AST)活性;试剂盒法检测大鼠肝组织中髓过氧化物酶(MPO)活性;ELISA法测定血清中血管紧张素转化酶(ACE)、血管紧张素转化酶2(ACE2)、血管紧张素II(AngII)、血管紧张素1-7(Ang-(1-7))的含量。Western blot检测肝组织中Ang II、Ang-(1-7)的蛋白含量。结果:治疗组较模型组和阻断剂组的肝损伤程度减轻;BML-111降低CCL4损伤的大鼠血清中ACE、AngII的含量(P<0.01)及升高血清中ACE2、Ang-(1-7)的含量(P<0.01)。BML-111增加肝组织中Ang-(1-7)含量,降低CCL4损伤的大鼠组织中AngII含量。结论:结果表明脂氧素受体激动剂BML-111对大鼠急性肝损伤的干预作用及其机制,可能与调节AngII和Ang-(1-7)有关。

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 50μg/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).