首页|18α-甘草次酸对斑马鱼急性毒性和对棕榈酸诱导的肝细胞脂质沉积的影响

18α-甘草次酸对斑马鱼急性毒性和对棕榈酸诱导的肝细胞脂质沉积的影响

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  • NETL
  • NSTL
  • 万方数据
目的:基于模式生物斑马鱼,考察18α-甘草次酸(GA)的急性毒性.评价18α-GA对棕榈酸(PA)诱导的肝细胞脂质沉积的影响.方法:选取发育正常斑马鱼进行18α-GA急性毒性评价,绘制"浓度-死亡率"曲线,计算半数致死浓度(LC50)、10％致死浓度(LC10)和最大非致死浓度(MNLC).考察不同浓度下,18α-GA对斑马鱼器官形态学结构畸形变化、运动情况异常变化和死亡数量等毒性表型的影响.采用PA诱导AML-12、HepG2及L02细胞,考察18α-GA对肝细胞脂质沉积的影响.结果:18α-GA对斑马鱼的LC50、LC10和MNLC分别为37、15、11 μmol/L.一定浓度的18α-GA可诱发斑马鱼心脏、肝脏、肾脏毒性、躯干/尾/脊索弯曲以及肠道毒性.与PA(300 μmol/L)组比较,18α-GA两浓度能够显著改善PA诱导的肝细胞胞质中脂质过量蓄积(P＜0.05,P＜0.01),10 μmol/L的18 α-GA能显著改善LDL、T-CHO及TG水平的异常升高(除HepG2细胞的T-CHO外)和HDL水平的异常降低(除HepG2细胞中HDL外)(P＜0.01).结论:斑马鱼急性毒性研究中,18α-GA具有潜在心脏、肝脏、肾脏和肠道组织毒性.18α-GA能够改善非酒精性脂肪肝病细胞模型脂质沉积.
Acute toxicity of 18α-glycyrrhetinic acid on zebrafish and effects of palmitic acid induced lipid deposition in hepatocytes
Objective:To investigate the acute toxicity of 18 α-glycyrrhetinic acid(GA)based on the model organism zebrafish.Meanwhile,the effect of 18 α-GA on palmitic acid-induced lipid deposition in hepatocytes was evaluated.Methods:The normal developing zebrafish were selected to evaluate the acute toxicity of 18 α-GA,and the'concentration-mortality'curve was drawn to calculate the half lethal concentration(LC50),10％lethal concentration(LC10)and maximum non-lethal concentration(MNLC)of zebrafish.The effects of 18 α-GA on the morphological changes of zebrafish organs,abnormal changes in movement,number of deaths and other toxic phenotypes were investigated at different concentrations.AML-12,HepG2 and L02 cells were induced by palmitic acid(PA),and the effects of 18 α-GA on the lipid deposition of hepatocytes were investigated.Results:The LC50,LC10 and MNLC of 18 α-GA on zebrafish were 37,15 and 11 μmol/L,respectively.Certain concentration of 18 α-GA could induce cardiotoxicity,hepatotoxicity,nephrotoxicity,trunk curvature and enterotoxicity in zebrafish.Compared with the PA(300 μmol/L)group,two concentration of 18 α-GA could significantly reduce the PA-induced excess lipid accumulation in the cytoplasm of hepatocytes(P＜0.05,P＜0.01),10 μmol/L 18 α-GA could significantly improve the abnormal increase of LDL,T-CHO and TG levels(except the T-CHO in HepG2 cell)and the abnormal decrease of HDL level(except the HDL in HepG2 cell)(P＜0.01).Conclusion:In the acute toxicity study of zebrafish,18 α-GA may have potential hepatotoxicity,cardiotoxicity,nephrotoxicity and intestinal toxicity.18 α-GA could improve lipid deposition in in vitro cell models of non-alcoholic fatty liver disease.

Glycyrrhetinic acid(GA)Non-alcoholic fatty liver disease(NAFLD)ZebrafishAcute toxicityLipid depositionPalmitic acid(PA)

樊亚东、王莹、柴润东、徐喆、赵泽宇、龚博炀、边育红

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天津中医药大学中西医结合学院,天津 301617

甘草次酸 非酒精性脂肪肝病 斑马鱼 急性毒性 脂质沉积 棕榈酸

国家重点研发计划天津市研究生科研创新基金项目天津中医药大学校级研究生创新基金项目天津中医药大学中西医结合学院院级研究生科研创新基金项目

2018YFC17065062020YJSB189YJSKC-20201003ZXYCXLX201907

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子：1.135
ISSN：1673-1727
年,卷(期)：2024.39(2)
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