期刊文献+

肝炎和肝硬化对肝脏UGTmRNA表达的影响

The influence of hepatitis and cirrhosis on the expression of UGTmRNA in liver tissues
下载PDF
导出
摘要 目的:探讨肝炎和肝硬化疾病对尿苷二磷酸葡萄糖醛酸基转移酶(UGT)表达水平的影响。方法:应用RT-PCR和Southern杂交技术,观察肝硬化和肝炎患者肝脏组织中UGT同工酶mRNA表达水平的差异,以及炎症和纤维化程度对UGT表达水平的影响。结果:与对照组比较,肝硬化组和肝炎组UGT2B15的mRNA的水平增高为210%和227%(P<0.05),UGT1A6的mRNA的水平增高为155%和166%(P>0.05)鸦纤维化对UGT2B15RNA的表达有显著的影响,与0级纤维化相比较,4、1、2级纤维化患者UGT2B15mRNA水平分别为172%、208%和243%,三级间差异有统计学意义(P<0.01);3、1、2级纤维化患者UGT2B7mRNA水平分别为192%、208%和156%,三者间差异无统计学意义(P>0.05)。炎症程度对大多数UGT同工酶的表达无明显影响。结论:肝炎和肝硬化可影响肝脏UGT同工酶的表达水平;纤维化对UGTmRNA的表达有显著的影响,炎症程度对大多数UGT同工酶的表达无明显影响。 Objective: To investigate the influence of hepatitis and cirrhosis on hepatic UGT isoforms expression. Methods: Reverse transcription and polymerase chain reaction(RT-PCR) and southern hybridization had been used to determine the mRNA levels of five UGT isoforms in hepatic tissues. Results: There was no significant correlation between human UGT mRNA levels and the plasma levels of bilirubin, ALT, ALP or GGT in patients with hepatitis or cirrhosis. Compared to control group, UGT2B15 mRNA level of cirrhosis group and hepatitis group increased by 210% and 227% respectively (P<0.05), UGT1A6mRNA level increased by 155% and 166% respectively(P>0.05). Compared to 0 cirrhotic grade patient, UGT2B15 mRNA level of 4,1,2 grade cirrhotic patients was 172%,208%and 243% respectively(P<0.01); UGT2B7 mRNA level of 3,1,2 grade cirrhotic patients was192%,208% and 156% respectively(P>0.05). Inflammation grade had no obvious affect on mRNA expression of most UGT isoforms. Conclusion: Hepatitis and cirrhosis can affect individual UGT isoform mRNA level. Degree of fibrosis has a significant affect on UGTmRNA expression; while the degree of inflammation has no obvious affect on mRNA expression of most UGT isoforms.
出处 《山东大学学报(医学版)》 CAS 北大核心 2005年第4期306-309,共4页 Journal of Shandong University:Health Sciences
关键词 肝炎 肝硬化 尿苷二磷酸葡糖醛酸基转移酶 Hepatitis Cirrhosis UDP-Glucuronosyltransferase
  • 相关文献

参考文献15

  • 1潘国宗.现代胃肠病学[M].北京:科学出版社,1994.1246.
  • 2Tukey RH, Strassburg CP. Human UDP-glucuronosyltransferases: metabolism, expression, and disease [J].Annu Rev Pharmacol Toxicol, 2000, 40:581-616.
  • 3Debinski HS, Mackenzie PI, Lee CS. UDP glucuronosyltransferase in human liver injury [J]. Gastroenterology,1996, 108:1 464-1 469.
  • 4cheuer PJ. Classification of chronic viral hepatitis:a need for reassessment[J]. J Hepatol, 1991, 13:372-374.
  • 5Nodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assesing histological activity in asymptomatic chronic active hepatitis[J]. Hepatology, 1981, 1:431-435.
  • 6Hoyumpa AM, Schenker S. Is glucuronidation truly preserved in patients with liver disease? [J]. Hepatology,1991, 13: 786-795.
  • 7Miner JO, Mackenzie PI. Drug glucuronidation in humans[J]. Pharmacology and Theapeutics, 1991, 51:347-369.
  • 8Furlan V, Demirdjian S, Bourdon O, et al. Glucuronidation of drugs by hepatic microsomes derived from healthy and cirrhotic human livers [J].Pharmacology,1999, 289:1 169-1 175.
  • 9Li YQ, Prentice DA, Howard ML. et al. Bilirubin and bile acids may modulate their own metabolism via regulating uridine diphosphate-glucuronosyltransferase expression in the rat [J]. J Gastroenterol Hepatol, 2000,15(8):865-870.
  • 10Secor JW. Schenker S. Drug metabolism in patients with liver disease[J]. Adv Intern Med, 1987, 104:379-405.

二级参考文献10

  • 1Mackenzie PI, Owens IS, Burchell B,et al. The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence[J]. Pharmacogenetics,1997,7: 255
  • 2Bissell DM,Guzelian PS. Phenotypic stability of adult rat hepatocytes in primary monolayer culture[J]. Ann N Y Acad Sci,1980,349: 85
  • 3Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction[J]. Anal Biochem,1987,162:156
  • 4Emi Y, Ikushiro S, Iyanagi T. Drug-responsive and tissue-specific alternative expression of multiple first exons in rat UDP-glucuronosyltransferase family 1 (UGT1) gene complex[J]. J Biochem (Tokyo),1995,117: 392
  • 5Strasser SI, Smid SA, Mashford M,et al. Sex hormones differentially regulate isoforms of UDP-glucuronosyltransferase[J].Pharm Res,1997,14:1115
  • 6Nemoto N and Sakurai J. Glucocorticoid and sex hormones as activating or modulating factors for expression of Cyp2b-9 and Cyp2b-10 in the mouse liver and hepatocytes[J]. Arch Biochem Biophys,1995,319: 286
  • 7Guzelian PS, Li D, Schuetz EG,et al. Sex change in cytochrome P-450 phenotype by growth hormone treatment of adult rat hepatocytes maintained in a culture system on matrigel[J]. Proc Natl Acad Sci U S A,1988,85: 9783
  • 8Gueraud F, Masmoudi T, Goudonnet H,et al. Differential effect of hypophysectomy and growth hormone treatment on hepatic glucuronosyltransferases in male rats: evidence for an action at a pretranslational level for isoforms glucuronidating bilirubin[J].Biochem Pharmacol,1997,53: 1637
  • 9Masmoudi T, Hihi AK, Vazquez M,et al. Transcriptional regulation by triiodothyronine of the UDP-glucuronosyltransferase family 1 gene complex in rat liver. Comparison with induction by 3-methylcholanthrene[J].J Biol Chem,1997,272: 17171
  • 10Goudonnet H, Magdalou J, Mounie A,et al. Differential action of thyroid hormones and chemically related compounds on the activity of UDP-glucuronosyltransferases and cytochrome P-450 isozymes in rat liver[J].Biochim Biophys Acta,1990,1035: 12

共引文献245

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部