中国药物警戒 ›› 2022, Vol. 19 ›› Issue (9): 977-981.
DOI: 10.19803/j.1672-8629.2022.09.10

• 基础与临床研究 • 上一篇    下一篇

吡嗪酰胺诱导L02细胞脂质过氧化的作用研究

刘梦醒, 刘媛, 杨敏, 罗季, 喻明丽, 王俊龙, 陈洁*   

  1. 昆明市第三人民医院药学部,云南 昆明 650041
  • 收稿日期:2021-03-05 出版日期:2022-09-15 发布日期:2022-09-16
  • 通讯作者: *陈洁,女,本科,主任药师,临床药理学。E-mail：ly869163966@163.com
  • 作者简介:刘梦醒,女,本科,中药师,中药学及临床药理学。
  • 基金资助:
    云南省科技计划青年项目基金（2017FD187）; 云南省科技计划青年项目基金（202001BA070001-092）; 昆明市卫生科技人才培养项目“千”工程（2020-SW[后备]-60）

Effects of pyrazinamide on lipid peroxidation in L02 cells

LIU Mengxing, LIU Yuan, YANG Min, LUO Ji, YU Mingli, WANG Junlong, CHEN Jie*   

  1. Department of Pharmacy, the Third People's Hospital of Kunming, Kunming Yunnan 650041, China
  • Received:2021-03-05 Online:2022-09-15 Published:2022-09-16

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摘要： 目的 研究吡嗪酰胺（pyrazinamide, PZA）对人正常肝细胞L02脂质过氧化反应的影响,探讨PZA肝损伤的作用机制。方法 用不同浓度的PZA溶液及N-乙酰-L-半胱氨酸（n-acetylcysteine, NAC）处理L02细胞,四甲基偶氮唑盐微量酶反应比色法（MTT法）检测PZA及NAC对L02细胞的影响;检测L02细胞内活性氧（reactive oxygen species, ROS）水平、丙二醛（malondialdehyde, MDA）含量及超氧化物歧化酶（superoxide dismutase, SOD）活性。结果 MTT结果显示,PZA作用L02细胞24、48、72 h的半数抑制浓度（IC50）分别为1 753.36、1 344.32、1 367.80 µg·mL-1,对细胞的抑制率具有一定浓度依赖性,其中3 125 µg·mL-1 PZA对细胞的抑制率有时间依赖性;与对照组比较,125、625 µg·mL-1 PZA组细胞内ROS含量显著升高;625、3 125 µg·mL-1 PZA组细胞内MDA含量显著升高;125、3 125 µg·mL-1 PZA组细胞内SOD活力显著降低;与单用PZA组比较,10 mmol·L-1 NAC+125、625 µg·mL-1 PZA组细胞内ROS含量有降低趋势;10 mmol·L-1 NAC+625、3 125 µg·mL-1 PZA组细胞内MDA含量显著降低;10 mmol·L-1 NAC+625、3 125 µg·mL-1 PZA组细胞内SOD活力有升高趋势。结论 PZA可降低L02细胞抗氧化系统能力,诱导L02细胞发生脂质过氧化反应,导致L02细胞凋亡,对肝细胞造成损伤。联合用药NAC后,可一定程度上减轻其肝损伤程度。

关键词: 吡嗪酰胺, L02细胞, MTT法, 脂质过氧化, 肝损伤

Abstract: Objective To study the lipid peroxidation of human normal hepatocyte L02 induced by pyrazinamide (PZA) and to explore the related mechanism of liver injury. Methods L02 cells were treated with different concentrations of PZA solution and N-acetyl-L-cysteine (NAC). The effects of PZA and NAC on L02 cells were detected by MTT, while the level of reactive oxygen species (ROS), the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in L02 cells were detected. Results MTT results showed that the 50% inhibitory concentration (IC50) of L02 cells treated with PZA for 24, 48 and 72 h was 1 753.36, 1 344.32 and 1 367.80 µg·mL-1, respectively, and the inhibition rate was concentration- dependent, but the inhibition rate of 3 125 µg·mL-1 PZA was time-dependent. Compared with the control group, the intracellular ROS content of the 125, 625 µg·mL-1 PZA group was significantly higher than that of the control group. The intracellular MDA content increased significantly in 625 and 3 125 µg·mL-1 PZA groups, but the intracellular SOD activity decreased significantly in 125,3 125 µg· µg·mL-1 PZA groups. Compared with PZA alone, the ROS content decreased in 10 mmol·L-1 NAC+125 and 625 µg· µg·mL-1 PZA groups, MDA content decreased significantly in 10 mmol·L-1 NAC+625 and 3 125 µg·mL-1 PZA groups, and SOD activity increased in 10 mmol·L-1 NAC+625 and 3 125 µg·mL-1 PZA groups. Conclusion PZA can reduce the ability of the antioxidant system of L02 cells, induce lipid peroxidation in L02 cells, lead to apoptosis of L02 cells and damage hepatocytes. The combined use of NAC can reduce the severity of liver injury to some extent.

Key words: pyrazinamide, L02 cells, MTT method, lipid peroxidation, liver injury

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