期刊文献+

罗格列酮和二甲双胍对大鼠非酒精性脂肪肝病的预防及机制研究 被引量:7

Preventive effects of rosiglitazone and metformin on nonalcoholic fatty liver disease in rats
原文传递
导出
摘要 目的 观察罗格列酮和二甲双胍对大鼠非酒精性脂肪肝病(NAFLD)的预防作用,并探讨其可能作用机理。方法 32只雄性SD大鼠分为4组:正常对照组、NAFLD对照组、罗格列酮干预组、二甲双胍干预组。以高脂饲料饲养诱发脂肪肝大鼠模型。12周末,处死所有动物,检测血脂、肝功能、肝脂质含量、肝组织病理学等,并检测血肿瘤坏死因子α(TNF-α)及肝组织TNF-α、肉毒碱软脂酰转移酶Ⅰ(CPT—Ⅰ)、乙酰辅酶A羧化酶(ACC)、脂肪酸合成酶(FAS)的mRNA表达等指标。结果 与NAFLD对照组比较,罗格列酮干预组及二甲双胍干预组的血TG(0.55±0.08,0.71±0.15 vs 0.85±0.15)mmol/L、ALT(49.1±7.4,56.0±33.6vs110.6±44.2)U/L及肝组织TG含量(33.7±8.2,37.2±7.8vs54.8±7.6)mg/g均显著下降(P均〈0.05),其肝脂肪变性及炎症程度亦显著减轻,其血清TNF-α(187.5±20.3,211.9±26.6vs324.2±34.2)pg/ml及肝组织TNF-α(0.35±0.12,0.49±0.18vs0.85±0.20)、FAS mRNA表达水平(0.34±0.13,0.45±0.15vs0.68±0.19)亦显著下降(P均〈0.05)。结论 罗格列酮和二甲双胍,可对高脂饲料饲养诱发的大鼠NAFLD产生保护作用;其保护作用与减少TNF-α和FAS表达有关。 Objective To investigate the preventive effects of rosiglitazone and metformin on nonalcoholic fatty liver disease (NAFLD) in rats, and explore the possible mechanisms involved. Methods Thirty-two male SD rats were randomized into normal control group, NAFLD control group, rosiglitazone-prevention and metformin-prevention groups. NAFLD rat model was established by feeding with high caloric diet. Serum TC, TG, ALT, AST, TNF-α, and liver lipid contents, liver histology and liver mRNA expressions of TNF-α, earnitine palmityl transferase - 1 (CPT-1). acyl- COA earboxylase (ACC) and fatty acid synthase (FAS) were assayed at the end of the 12 th week. Results Compared with NAFLD control group, rosiglitazone-prevention and metformin-prevention groups serum TC(0. 55±0. 08,0. 71±0. 15 vs 0.85±0.15)mmol/L, ALT(49.1±7.4,56.0±33.6 vs 110. 6±44. 2)U/L, and liver TG(33.7±8. 2, 37.2±7.8 vs 54.8±7.6)mg/g decreased significantly (P〈0. 05) ; fatty denaturation of liver tissues and hepatic inflammation markedly reduced; and serum TNF-α(187.5±20. 3,211.9±26.6 vs 324.2±34. 2)pg/ml and liver TNF-α(0. 35±0. 12,0. 49±0. 18 vs 0. 85 ± 0. 20), FAS mRNA (0. 34 ± 0. 13,0. 45 ± 0. 15 vs 0. 68± 0. 19)also decreased significantly (P〈0. 05). Conclusions Rosiglitazone and metformin have protective effects on NAFLD in rats, and these effects may be related to the decreased expressions of TNF-α and FAS.
出处 《中华老年医学杂志》 CAS CSCD 北大核心 2007年第1期51-55,共5页 Chinese Journal of Geriatrics
基金 国家人事部博士后基金(2004036431)
关键词 脂肪肝 非酒精性 预防 胰岛素抵抗 Fatty liver, nonalcoholic disease Prevention Insulin resistance
  • 相关文献

参考文献13

  • 1Bloomgarden ZT.Second World Congress on the Insulin Resistance Syndrome:insulin resistance syndrome and nonalcoholic fatty liver disease.Diabetes Care,2005,28:1518-1523.
  • 2Lin HZ,Yang SQ,Chuckaree C,et al.Metformin reverses fatty liver disease in obese,leptin-deficient mice.Nat Med,2000,6:998-1003.
  • 3Caldwell SH,Hespenheide EE,Redick JA,et al.A pilot study of a thiazolidinedione,troglitazone,in nonalcoholic steatohepatitis.Am J Gastroenterol,2001,96:519-525.
  • 4蒙碧辉,梁世坤,黄松,冼苏,舒昌达.国产罗格列酮对实验性树肝脂肪变性的保护作用[J].中华消化杂志,2003,23(12):718-722. 被引量:6
  • 5范建高,钟岚,王国良,汪佩文,徐正婕,靖大道,张丕利.胰岛素抵抗在高脂饮食大鼠非酒精性脂肪性肝炎发病中的作用[J].胃肠病学,2000,5(3):169-170. 被引量:17
  • 6Eldershaw TP,Rattigan S,Cawthorne MA,et al.Treatment with the thiazolidinedione (BRL 49653)decreases insulin resistance in obese Zucker hindlimb.Horm Metab Res,1995,27:169-172.
  • 7Zhang XF,Tan BK.Effects of an ethanolic extract of Gynura procumbens on serum glucose,cholesterol and triglyceride levels in normal and streptozotocin-induced diabetic rats.Singapore Med J,2000,41:9-13.
  • 8Kanauchi M.A new index of insulin sensitivity obtained from the oral glucose tolerance test applicable to advanced type 2 diabetes.Diabetes Care,2002,25:1891-1892.
  • 9Xu A,Wang Y,Keshaw H,et al.The fat-derived hormone adiponectin alleviated alcoholic and nonalcoholic fatty liver disease in mice.J Clin Invest,2003,112:91-100.
  • 10Li Z,Yang S,Lin H,et al.Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver diasease.Hepatology,2003,37:343-350.

二级参考文献19

  • 1Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis:summary of an AASLD Single Topic Conference. Hepatology, 2003,37: 1202-1219.
  • 2Braissant O, Foufelle F, Scotto C, et al. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.Endocrinology, 1996, 137: 354-366.
  • 3Kono H, Arteel GE, Rusyn I, et al. Ebselen prevents early alcoholinduced liver injury in rats. Free Radic Biol Med, 2001, 30:403-411.
  • 4Diehl AM. Cytokines and the molecular mechanisms of alcoholic liver disease. Alcohol Clin Exp Res, 1999, 23: 1419-1424.
  • 5Nanji AA, Jokelainen K, Tipoe GL, et al. Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration. J Pharmacol Exp Ther, 2001,299: 638-644.
  • 6Kon K, Ikejima K, Hirose M, et al. Pioglitazone prevents earlyphase hepatic fibrogenesis caused by carbon retrachloride. Biochem Biophys Res Commun, 2002, 291: 55-61.
  • 7Sung CK, She H, Xiong S, et al. Tumor necrosis factor-alpha inhibits peroxisome proliferator-activated receptor gamma activity at a posttranslational level in hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol, 2004, 286: G722-G729.
  • 8李毅夫,赵水平.胰岛素抵抗综合征.见赵水平主编,临床血脂学[M].长沙:湖南科技出版社,1997:137~151
  • 9Garg A. Insulin resistance in the pathogenesis of dyslipidemia. Diabetes Care, 1996, 19: 387~389.
  • 10Diehl AM. Nonalcoholic steatohepatitis. Semin Liver Dis, 1999, 19: 221~229.

共引文献33

同被引文献79

引证文献7

二级引证文献56

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