张志超李妤丁琳柳军△ 尚靖△.不同来源肝细胞在体外降脂药物评价中药效反应的对比[J].,2014,14(5):850-853 |
不同来源肝细胞在体外降脂药物评价中药效反应的对比 |
In-vitro Evaluation and Comparison of the Lipid-lowering DrugsPharmacological Response on Liver Cells of Different Origin |
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DOI: |
中文关键词: HepG2 细胞 原代大鼠肝细胞 脂质沉积 氧化应激 |
英文关键词: HepG2 cell Primary rat hepatocytes Hepatic steatosis Oxidative Stress |
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中文摘要: |
摘要目的:通过对比不同来源的人肝癌细胞系HepG2 和原代大鼠肝细胞在体外降脂药物评价中药效反应,指导两种肝细胞在体
外降脂药物评价中的实际应用。方法:用游离脂肪酸(油酸/ 棕榈酸,2:1)诱导HepG2 细胞、原代大鼠肝细胞脂肪变性,并用100
滋mol·L-1苯扎贝特干预,检测细胞内甘油三酯(TG)、总胆固醇(TC)、活性氧(ROS)含量,细胞内脂滴数目、并检测细胞上清液中
丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果:FFA 刺激使HepG2 细胞和原代大鼠肝细胞脂质沉积(TG、脂滴)和氧化
应激(ROS、MDA、SOD)水平上升。苯扎贝特对HepG2细胞1 mmol·L-1 FFA 造模组和原代大鼠肝细胞0.5 mmol·L-1 FFA 造模组
脂质沉积和氧化应激水平改善显著;而HepG2 细胞0.5 mmol·L-1 FFA 造模组和原代大鼠肝细胞1 mmol·L-1 FFA 造模组脂质沉积
和氧化应激水平在苯扎贝特干预后变化不明显。结论:在相同FFA 造模浓度,原代大鼠肝细胞病理特征变化更为明显;苯扎贝特
对两种肝细胞在脂质沉积和氧化应激水平的作用也不完全相同。因而HepG2 细胞和原代大鼠肝细胞在体外降脂药物评价中药效
反应是不完全相同的。 |
英文摘要: |
ABSTRACR Objective:To guide the application of the two kinds of liver cells in vitro evaluation of lipid-lowering drugs through
evaluate the lipid lowering effects of bezafibrate on liver cells fromdifferent origin with free fatty acids model in-vitro. Methods: Hepatic
steatosis was induced in HepG2 cells and primary rat hepatocytes by using free fatty acids (oleic acid / palmitic acid, 2:1) model. Lipid
lowering effects of bezafibrate (100滋mol·L-1) were analyzed by detecting various parameters: intracellular triglyceride (TG), total cholesterol
(TC) and the lipid contents within cells. Further, Reactive oxygen Species (ROS), malondialdehyde (MDA) and antioxidant enzymes
(SOD) were examined as oxidative stress markers. Results:Hepatic steatosis (TG, lipid droplet) and Oxidative Stress (ROS, MDA, SOD)
were increased with FFA treatment. Bezafibrate significantly ameliorate the hepatic steatosis and Oxidative Stress in HepG2 cells induced
by 1 mmol·L-1 FFA and primary rat hepatocytes induced by 0.5 mmol·L-1 FFA model. Howerever, bezafibrate have no significant ameliorative
effect on HepG2 cells induced by 0.5 mmol·L-1 FFA and primary rat hepatocytes induced by 1 mmol·L-1 FFA model.
Conclusion:In FFA induced hepatic steatosis model, disease pathological features are clearer in rat primary hepatocytes as compared to HepG2 cells.
Moreover, pharmacological effects of bezafibrate are more significantly expressed at 1 mmol·L-1 FFA induction in HepG2 and 0.5
mmol·L-1 FFA induction in rat primary hepatocytes. In-Conclusion pharmacological activity of lipid lowering drugs may differ in
response when tested on HepG2 cells and primary rat hepatocytes at least in FFA model. |
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