海狗油对非酒精性脂肪肝肝细胞色素P450 2E1表达及与氧化抗氧化关系的影响

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (7): 755-758.

海狗油对非酒精性脂肪肝肝细胞色素P450 2E1表达及与氧化抗氧化关系的影响

邓利娟, 李湛军, 乐嘉静, 阎安庄, 徐康森

中国药品生物制品检定所生化药品与基因工程药物室, 北京100050

收稿日期:2004-04-21 修回日期:2004-05-14 出版日期:2004-07-26 发布日期:2020-11-20
通讯作者: 邓利娟,女,硕士,助理研究员,主要从事生化药理与生物检定。Tel:010-67017755-464 E-mail:lisadeng06@hotmail.com

Effects of seal oil on the correlation between hepatocyte cytochrome P450 2E1 expression and oxidation, antioxidation in rats with nonalcoholic fatty liver

DENG Li-Juan, LI Zhan-Jun, LE Jia-Jing, YAN An-Zhuang, XUN Kang-Sen

Division of Biochemical Drug and Genetic Engineering Pharmaceutical, National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China

Received:2004-04-21 Revised:2004-05-14 Online:2004-07-26 Published:2020-11-20

摘要/Abstract

摘要： 目的: 研究海狗油对非酒精性脂肪肝肝细胞色素P450 2E1表达及与氧化抗氧化关系的影响。方法: 于实验d 1 一次性皮下注射小剂量四氯化碳并长期喂食高脂饲料复制大鼠脂肪肝模型,7 周后,开始分别口服灌胃(ig)给予模型组等体积橄榄油,阳性药辛伐他汀4mg·kg^-1,海狗油各组ig 海狗油0.5、1.6和4.8g·kg^-1,每天1次,连续8周。观察肝组织病理形态的变化和肝细胞色素P450 2E1的表达;测定血清和肝内丙二醛(MDA)、超氧化物歧化酶(SOD)以及游离脂肪酸(FFA)含量的变化。结果: 与脂肪肝模型组比较,海狗油不同给药组病理切片苏丹Ⅲ染色和HE 染色显示肝细胞的脂变程度明显减轻,脂滴减少,免疫组化证明肝细胞色素P450 2E1表达受到不同程度的抑制,同时血清及肝内MDA、FFA显著降低,SOD活性升高。在模型组和各给药组不同的肝组织内,CYP2E1的表达强度及分布的方式存在着差异。结论: 海狗油能显著抑制大鼠脂肪肝CYP2E1的表达,减轻脂质过氧化反应。动物个体间存在CYP2E1多态性。

关键词: 海狗油, 脂肪肝, 细胞色素P450, 免疫组化, 脂质过氧化

Abstract: AIM: To explore the effects of seal oil on the correlation between hepatocyte cytochrome P450 2E1 expression and oxidation, antioxidation in rats with nonalcoholic fatty liver.METHODS: After 7 weeks the fatty liver models were induced by onetime subcutaneous injecting a low dose of carbon tetrachloride on the first day and chronically feeding with high fat diet in rats.The rats in the model group, simvastatin group and different doses seal oil group were taken by olive oil in the same volume of seal oil, 4 mg·kg^-1 simvastatin, and 0.5,1.6 and 4.8g·kg^-1 seal oil respectively once a day for 8 weeks.Changes on pathology of liver and expression of hepatocyte cytochrome P450 2E1 were observed.MDA, SOD and FFA in the liver and serum were measured by biochemical analysis.RESULTS: Compared with model group, the fatty degeneration of liver reduced and a smaller lipid droplet of liver in seal oil group.The hepatocyte cytochrome P450 2E1 expression was inhibited.Meanwhile contents of MDA and FFA were significantly decreased but SOD contents were significantly increased in serum and liver.The intensity and distribution of CYP 2E1 express between rats of model differed.These differences existed in simvastatin group and different doses seal oil group.CONCLUSION: Seal oil can inhibit the hepatocyte cytochrome P450 2E1 expression in rats with fatty liver and reduce lipid peroxidation.There is genetic polymorphism of cytochrome P450 2E1 between rats.

Key words: seal oil, fatty liver, cytochrome P450, immunohistochemistry, lipid superoxidation

中图分类号:

R963

邓利娟, 李湛军, 乐嘉静, 阎安庄, 徐康森. 海狗油对非酒精性脂肪肝肝细胞色素P450 2E1表达及与氧化抗氧化关系的影响[J]. 中国临床药理学与治疗学, 2004, 9(7): 755-758.

DENG Li-Juan, LI Zhan-Jun, LE Jia-Jing, YAN An-Zhuang, XUN Kang-Sen. Effects of seal oil on the correlation between hepatocyte cytochrome P450 2E1 expression and oxidation, antioxidation in rats with nonalcoholic fatty liver[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(7): 755-758.

[1]	朱丽, 魏兵, 廖世峨, 张超, 郑晓宇, 刘亚军. 药物代谢酶细胞色素P450单核苷酸多态性影响哮喘儿童吸入皮质醇激素疗效研究[J]. 中国临床药理学与治疗学, 2023, 28(5): 536-543.
[2]	王凯, 宋敏, 宋志靖, 李金益. 血管内皮细胞铁死亡在椎动脉型颈椎病中的作用机制[J]. 中国临床药理学与治疗学, 2022, 27(5): 588-594.
[3]	张亮, 廖勇群, 夏秦川, 周诗侗, 李小丽. 铁死亡调控信号通路以及在相关疾病中的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(2): 227-234.
[4]	吴懿, 方芳, 陈瑛, 樊军卫. 供受体CYP3A5基因型对肝移植术后早期他克莫司谷浓度的影响作用及其临床意义[J]. 中国临床药理学与治疗学, 2021, 26(6): 631-639.
[5]	吴茂锋, 刘畅, 戴慧晖, 麦长凤, 黄丹丽, 缪经纬, 刘丽忠, 方翼. pazopanib血药浓度个体差异与细胞色素P450 3A4基因多态性的关系初探[J]. 中国临床药理学与治疗学, 2020, 25(12): 1376-1380.
[6]	方川川，倪观太，金兰, 刘记, 刘晓庆，乔春, 罗永红. PEA-15 磷酸化状态与卵巢上皮性癌预后的相关分析[J]. 中国临床药理学与治疗学, 2019, 24(5): 523-528.
[7]	陈曦，凌嘉伟，丁嘉欣，江振洲，张陆勇. 他莫昔芬诱导非酒精性脂肪肝的机制研究进展[J]. 中国临床药理学与治疗学, 2018, 23(6): 715-720.
[8]	彭秋菊，严华成，石磊. 细胞色素P450 SNP与冠心病易感性关系的研究进展[J]. 中国临床药理学与治疗学, 2018, 23(4): 477-480.
[9]	周红萍，杨兴鑫，庄让笑，邵益丹，席建军，廖莉，任白鹭，王萍萍，余舒莹，史婷婷. N-乙酰半胱氨酸活性炭缓释微囊对幼鼠非酒精性脂肪肝病miRNA的影响[J]. 中国临床药理学与治疗学, 2018, 23(3): 263-270.
[10]	肖鹏，梅家转，白桦，栗敏，刘桂举，李瑞君，沈杰. 细胞色素P450 1A1基因多态性对奥沙利铂联合卡培他滨方案治疗结直肠癌患者临床疗效的影响[J]. 中国临床药理学与治疗学, 2018, 23(2): 159-164.
[11]	张培玉，任静，职文倩，刘澄铭，郜娜. 和厚朴酚等五种中药有效成分对CYP酶活性的体外抑制作用[J]. 中国临床药理学与治疗学, 2017, 22(8): 922-926.
[12]	刘晶晶, 梁智, 罗详冲, 何功浩, 冯恩富, 徐贵丽. LC-MS/MS法同时测定大鼠血浆中4种CYP450探针药物浓度[J]. 中国临床药理学与治疗学, 2017, 22(2): 144-150.
[13]	韦艺丹，许美娟，季晖. 花生四烯酸的ω-羟化代谢途径与心脑血管疾病[J]. 中国临床药理学与治疗学, 2016, 21(7): 826-833.
[14]	何新康, 叶夷露，潘蓓蓓，俞洁，刘丹丹. 西红花素对大鼠脑缺血再灌注损伤的神经保护作用及神经行为学影响[J]. 中国临床药理学与治疗学, 2016, 21(3): 282-286.
[15]	贾元威，沈杰，谢海棠，黄锐. 天麻素对人肝微粒体细胞色素P450酶的抑制作用[J]. 中国临床药理学与治疗学, 2016, 21(2): 134-138.