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细胞色素P450 2E1在脂肪性肝炎大鼠肝组织的表达及作用 被引量:2

The expression of cytochrome P450 2E1 in liver tissues in rats with steatohepatitis
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摘要 目的探讨细胞色素P4502E1(CYP2E1)在脂肪性肝炎大鼠肝组织内的表达和作用。方法通过高脂饮食和逐渐增加酒精灌胃量持续16周建立Wister大鼠脂肪性肝炎动物模型,造模结束时检测模型组和正常组动物血脂、游离脂肪酸(FFA)和肝组织丙二醛(MDA)、超氧化物歧化酶(SOD)、还原性谷胱甘肽(GSH)含量;免疫组化标记检测肝组织CYP2E1表达;RT-PCR法检测CYP2E1 mRNA的水平。结果实验结束时,模型组大鼠血脂和血清FFA较正常组显著增高(P<0.01);肝组织MDA较正常组显著增高(P<0.01),而SOD和GSH较正常组明显减低(P<0.01);肝组织内CYP2E1及其基因表达较正常组显著升高(P<0.01),并与肝组织内MDA、脂肪变程度、炎症计分呈明显正相关(r值分别为0.652,0.913和0.943,P值均<0.05),与SOD、GSH呈显著负相关(r值分别为-0.916,-0.766,P<0.01)。结论脂肪性肝炎大鼠肝脏内CYP2E1呈诱导表达状态,后者可能通过增强氧应激,降低抗氧化能力,加重脂质过氧化等过程参与了脂肪性肝炎的形成。 Objective To investigate the expression and effects of cytochrome P450 2E1 in rats with steatohepatitis. Methods Steatohepatitis model was established by feeding high fat diet and increasingly intragastric perfusion of ethanol in rats for 16 weeks. Blood lipids, free fatty acid in serum and the malonaldehyde, superoxide dismutase and glutathione in liver were measured respectively; CYP2E1 and its mRNA in liver specimens were detected by immunohistochemistry and RT-PCR, respectively. Results Blood lipids ,serum free fatty acid in rats with steatohepatitis was markedly increased (P〈0. 01) ; the level of malonaldehyde increased significantly(P〈0.01 ), whereas superoxide dismutase and glutathione concentration was markedly decreased in model group (P〈0.01). The expression of CYP2E1 and its mRNA was enhanced significantly(P〈0.01) in rats with steatohepatitis. Conclusion CYP 2E1 increases in rat with steatohepatitis, which might improve oxygen stress, decrease anti-oxygen ability and aggravate lipid peroxidation.
出处 《实用肝脏病杂志》 CAS 2007年第6期369-372,共4页 Journal of Practical Hepatology
关键词 脂肪性肝炎 细胞色素P450 2EI 脂质过氧化 大鼠 Steatohepatitis Cytochrome P450 2E1 Lipid peroxidation Rats
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  • 1王宝恩,王志富.实验性免疫性肝纤维化模型的研究[J].中华医学杂志,1989,69(9):503-505. 被引量:145
  • 2王小亚 纪小龙.免疫组化的理论和技术.诊断免疫组织化学[M].北京:军事医学科学出版社,1997.14-16.
  • 3Yang SQ, Zhu H, Li Y, et al. Mitochondrial adaptation to obesity related oxidant stress. Arch Biochem Biophys, 2000, 378: 259-268.
  • 4Morris DL, Davila JC. Analysis of rat cytochrome P450 iso-enzyme expression using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Biochem Pharmacol, 1996, 52:781-792.
  • 5Niemela O, Parkkila S, Juvonen RO, et al. Cytochromes P450 2A6,2E1, and 3A and production of protein-aldehyde addicts in the liver of patients with alcoholic and non-alcoholic liver diseaes. J Hepatol,2000, 33: 893-901.
  • 6Rouach H, Fataccioli V, Gentil, et al. Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. Hepatology, 1997, 25:351-355.
  • 7Weltman MD, Farrekk GC, Hall P, et al. Hepatic cytochromes P450 2E1 is increased in patients with nonalcoholic steatohepatis.Hepatology, 1998, 27: 128-133.
  • 8范建高,国外医学.消化系统疾病分册,1997年,17卷,92页
  • 9倪燕君,国外医学.消化系统疾病分册,1997年,17卷,158页
  • 10范建高,肝脏,1996年,1卷,215页

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  • 1张评浒,张娟,高逸湘,钟民,尚靖,张陆勇.中国华东汉族人群细胞色素酶CYP3A4新基因型的发现与序列分析[J].中国临床药理学与治疗学,2008,13(10):1154-1157. 被引量:1
  • 2刘晨晖,乐江.细胞色素P450 CYP2E1酶构型特征及其表达调控机制的研究进展[J].中国药理学与毒理学杂志,2010,24(2):155-160. 被引量:26
  • 3龚建平,高长明,Takezaki Toshiro,吴建中,陈敏斌,曹海霞,曹佳,Hamajima Nobuyuki,Tajima Kazuo,周建农.细胞色素P450 2E1基因多态性、烟酒习惯与直肠癌易感性的关系[J].南京医科大学学报(自然科学版),2006,26(12):1163-1167. 被引量:6
  • 4成碟,徐为人,刘昌孝.细胞色素P450(CYP450)遗传多态性研究进展[J].中国药理学通报,2006,22(12):1409-1414. 被引量:44
  • 5Hasler JA. Pharmacogenetics of cytochromes P450 [J]. Mol Aspects Med, 1999, 20(1-2) : 12-137.
  • 6Wang SL, Lee H, Chen KW, et al. Cytochrome P4502E1 genetic polymorphisms and lung cancer in a Taiwan Residents population[J]. Lung Cancer, 1999, 26:27-34.
  • 7Hayashi S, Watamabe J, Kawajiri K. Genetic polymor- phisms in the 5'-flanking region change transcriptional relation of the human cytochrome P4502E1 gene [J]. J Biochem, 1991,110(4) : 559-565.
  • 8Gonzalez FJ. Role of cytochromes P450 in chemical toxi- city and oxidative stress: studies with CYP2E1 [J]. Mu- tat Res, 2005, 569(122): 101-110.
  • 9Miller GP. Advances in the interpretation and prediction of CYP2EI metabolism from a biochemical perspective [J]. Expert Opin Drug Metab Toxicol, 2008, 4(8): 1053-1064.
  • 10Porubsky PR, Meneely KM, man cytochrome P450 2E1. Scott EE. Structures of hu- Insights into tile binding of inhibitors and both small molecular weight and fatty acid substrates [J]. J Biol Chem, 2008, 283 (48): 33698- 33707.

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