目的 探讨microRNA-122(miR-122)在非酒精性脂肪肝病(non-alcoholic fatty liver disease, NAFLD)患者血清中的表达及其临床意义。方法 采用荧光定量RT-PCR技术检测健康人、高脂血症患者、非酒精性单纯性脂肪肝(non-alcoholic simply fatty liver, NAFL)及非酒精性脂肪性肝炎(non-alcoholic steatohepatitis, NASH)患者血清中miR-122的表达。结果 各组miR-122的表达水平分别为5.94±1.21(2-△△Ct), 5.99±1.03(2-△△Ct), 8.67±0.72(2-△△Ct), 10.55±0.83(2-△△Ct)。高脂血症患者和健康人血清中miR-122的表达量差异无统计学意义(P＞0.05)。与前两组相比, NAFL和NASH患者血清中miR-122的表达明显逐渐升高, 差异有统计学意义(P<0.05)。结论 非酒精性脂肪肝病患者血清中miR-122的表达量明显升高, 提示miR-122参与了非酒精性脂肪肝的形成及进展过程, 可作为诊断和评估组织学病变严重性的一种新的生物学指标, 同时有望成为一个潜在的治疗靶点。
Abstract
Objective To analyze the expression levels of serum microRNA-122 (miR-122) in non-alcoholic fatty liver disease (NAFLD) patients, and its clinical significance. Methods Patients with normal liver, hyperlipidemia, non-alcoholic simply fatty liver(NAFL), non-alcoholic steatohepatitis(NASH)were included in this study. Blood samples of the patients were collected for analysis. Real time quantitative PCR technique was used to measure the expression level of serum miR-122. Results The expression levels of serum miR-122 was 5.94±1.21(2-△△Ct), 5.99±1.03(2-△△Ct), 8.67±0.72(2-△△Ct)and 10.55±0.83(2-△△Ct), respectively. The difference in the expression level between normal liver and hyperlipidemia patients was not statistically significant. Comparing with normal liver and hyperlipidemia patients, miR-122 presented higher expressions in NAFL patients(P<0.05), especially in NASH patients. Conclusion miR-122 plays an important role in NAFLD development and has early diagnostic value for indicating NAFLD. It may also be a potential therapeutic target in NAFLD with significant clinical value.
关键词
非酒精性脂肪性肝病 /
脂肪代谢 /
早期诊断 /
miR-122
Key words
NAFLD /
fatty acid metabolism /
early diagnosis /
miR-122
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Brunt E M. Pathology of nonalcoholic fatty liver disease[J].Nat Rev Gastroenterol Hepatol, 2010, 7:195-203.
[2] Jopling C. Liver-specific microRNA-122:biogenesis and function[J].RNA Biol, 2012, 9(2):1-6.
[3] Elmen J, Lindow M, Silahtaroglu A, et al. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver[J].Nucleic Acids Res, 2008, 36(4):1153-1162.
[4] Esau C, Davis S, Murray S F, et al. miR -122 regulation of lipid metabolism revealed by in vivo antisense targeting [J].Cell Metab, 2006, 3(2):87-98.
[5] 中华医学会肝脏病学分会脂肪肝和酒精性肝病学组. 非酒精性脂肪性肝病诊疗指南[J].中国肝脏病杂志(电子版), 2010, 2(4):43-48.
[6] 中国成人血脂异常防治指南制定联合委员会. 中国成人血脂异常防治指南[J]. 中华心血管病杂志, 2007, 35(5):390-419.
[7] Livak K J, Schmittgen T D.Analysis of relative gene expression data using real-time quantitative PCR and the 2[-Delta Delta C(T)] Method[J].Methods, 2001, 25(4):402-408.
[8] Bartel D P. MicroRNAs: genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116:281-297.
[9] Ambros V. The functions of animal microRNAs[J].Nature, 2004, 431(7006):350-355.[10] Moore K J, Rayner K J, Suárez Y, et al. microRNAs and cholesterolmetabolism[J]. Trends Endocrinol Metab, 2010, 21(12): 699-706.
[11] Fernandez-Hernando C, Suarez Y, Rayner K J, et al. MicroRNAs in lipid metabolism[J]. Curr Opin Lipidol, 2011, 22(2): 86-92.
[12] Gerin I, Clerbaux L A, Haumont O, et al. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation[J]. J Biol Chem, 2010, 285(44):33652-33661.
[13] Krutzfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNA in vivo with 'antagomirs'[J]. Nature, 2005, 438(7068):685-689.
