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氟伐他汀钠对斑马鱼肝抗氧化体系及肝功能的影响

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目的 研究氟伐他汀钠(FLU)对斑马鱼肝内抗氧化体系和肝功能的影响.方法 采用半静态暴露法,以氟伐他汀钠为研究对象,选取斑马鱼为指示生物,将斑马鱼分别暴露在空白对照组和 0.004、0.04、0.4 mg/L的氟伐他汀钠溶液中,于暴露 48 h 后,取样检测氟伐他汀钠对斑马鱼肝内 ROS 含量和抗氧化酶 SOD、CAT、GPx、GST 的活性,同时检测肝功能指标 ALT、AST的活性.结果 与对照组相比,氟伐他汀钠暴露 48 h后,中、高浓度的氟伐他汀钠会造成 ROS含量显著性升高(P<0.01),CAT、SOD、CuZn-SOD、GPx 的活性变化具有同步性,但低浓度的氟伐他汀钠对所有的抗氧化酶均无显著的激活或抑制作用.中浓度的氟伐他汀钠对 CAT、SOD 具有激活作用(P<0.01),高浓度的氟伐他汀钠对抗氧化酶SOD、CAT、GPx、GST都有激活作用(P<0.05,P<0.01),同时对ALT和AST也具有显著性的激活作用(P<0.01).分子对接结果表明氟伐他汀钠能够与斑马鱼 CAT 蛋白对接,最佳对接位点为Met392,对接能量为-4.63 kcal/mol.结论 随着药物浓度的升高,氟伐他汀钠能够对斑马鱼肝内抗氧化体系和肝功能造成影响.
Effect of Fluvastatin Sodium on the Antioxidant System and Liver Function of Zebrafish Liver
Objective To study the effects of fluvastatin sodium on the antioxidant system and liver function in the liver of zebrafish.Method Using a semi-static exposure method,zebrafish were selected as indicator organisms and exposed to blank control group and 0.004,0.04 and 0.4 mg/L of fluvastatin sodium solution,and samples were taken at 48 h after exposure to detect the effects of fluvastatin sodium on ROS content and activities of antioxidant enzymes SOD,CAT,GPx and GST in zebrafish liver.The activities of liver function indexes ALT and AST were also measured.Result Compared with the control group,the medium and high concentrations of fluvastatin sodium caused a significant increase in ROS content compared with the control group after 48 h exposure(P<0.01),and the activities of CAT,SOD,CuZn-SOD,and GPx changed synchronously,but the low concentration of fluvastatin sodium had no significant activation or inhibition effect on all antioxidant enzymes.Medium concentrations of fluvastatin sodium had activating effects on CAT and SOD(P<0.01),and high concentrations of fluvastatin sodium had activating effects on all antioxidant enzymes(P<0.05,P<0.01),while high concentrations of fluvastatin sodium had significant activating effects on ALT and AST(P<0.01).The molecular docking result showed that fluvastatin sodium was able to dock with zebrafish CAT protein,with the optimal docking site being Met392 and docking energy of-4.63 kcal/mol.Conclusion With increasing drug concentrations,fluvastatin sodium was able to affect the antioxidant system and liver function in zebrafish liver.

fluvastatin sodiumzebrafishantioxidant systemliver functionmolecular docking

王贤锐、牟全玲、李小龙、史嘉烨、李茹萌、丁存宝

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华北理工大学生命科学学院,唐山 063210

氟伐他汀钠 斑马鱼 抗氧化体系 肝功能 分子对接

河北省教育厅自然科学研究项目河北省卫生计生委医学科学研究课题唐山市科技局项目

QN20150672017019622150206

2024

实验动物科学
北京实验动物研究中心 北京实验动物学学会 北京实验动物管理办公室

实验动物科学

CSTPCD
影响因子:0.603
ISSN:1006-6179
年,卷(期):2024.41(2)
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