丙型肝炎病毒感染患者血清外泌体miR-122的表达量及临床意义探讨
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摘要
目的探讨血清外泌体微小RNA-122 (miR-122)在丙型肝炎病毒(HCV)感染者中的表达水平及其临床意义。方法收集40例HCV患者,其中28例为HCV-1b,12例为非HCV-1b,检测血清循环和外泌体miR-122的表达水平以及其他的生化指标。同时选择20例健康人作对照。结果HCV组血清外泌体中的miR-122的表达量均较健康对照组低,但HCV-1b组的miR-122表达量比非HCV-1b组略高,其次HCV组血清外泌体miR-122的表达量与谷草转氨酶(AST)或谷丙转氨酶(ALT)的表达量呈负相关,但相关性弱;血清外泌体中的miR-122的表达趋势与血清循环miR-122一致;此外,血清循环miR-122在持续病毒应答率(SVR)患者中表达量明显高于非持续病毒应答率(NR)患者(P <0. 05),但血清外泌体miR-122在SVR患者和NR患者中表达量差异无统计学意义。结论血清外泌体miR-122可能可以预测肝损伤,但暂不认为其能预测HCV治疗效果。
Objective To investigate the expression and the clinical function of exosomal miR-122 in patients with hepatitis C( HCV). Methods Forty HCV patients( 28 HCV-1b and 12 non-HCV-1b) were enrolled in this study,serum and exosomal miR-122 and other conventional biomarkers reflecting liver function were measured. 20 healthy subjects were enrolled as control. Results The expressions of exosomal miR-122 in HCV-1b and nonHCV-1b groups were higher than that in healthy group,but the former was slightly higher than the latter. Exosomal miR-122 in HCV group was weakly negatively related to AST and ALT levels. The expression of exosomal miR-122 was consistent with that of serum miR-122. Besides,the serum miR-122 in sustained virological response( SVR)group was higher than that in non-sustained virological response( NR) group( P < 0. 05),but statistical difference of exosomal miR-122 between SVR and NR groups was not found. Conclusion In HCV patients,exosomal miR-122 may be useful in evaluating hepatic impairment,but it cannot be used to evaluate the therapeutic effect.
Objective To investigate the expression and the clinical function of exosomal miR-122 in patients with hepatitis C( HCV). Methods Forty HCV patients( 28 HCV-1b and 12 non-HCV-1b) were enrolled in this study,serum and exosomal miR-122 and other conventional biomarkers reflecting liver function were measured. 20 healthy subjects were enrolled as control. Results The expressions of exosomal miR-122 in HCV-1b and nonHCV-1b groups were higher than that in healthy group,but the former was slightly higher than the latter. Exosomal miR-122 in HCV group was weakly negatively related to AST and ALT levels. The expression of exosomal miR-122 was consistent with that of serum miR-122. Besides,the serum miR-122 in sustained virological response( SVR)group was higher than that in non-sustained virological response( NR) group( P < 0. 05),but statistical difference of exosomal miR-122 between SVR and NR groups was not found. Conclusion In HCV patients,exosomal miR-122 may be useful in evaluating hepatic impairment,but it cannot be used to evaluate the therapeutic effect.
引文
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[14]Bihrer V,Friedrich-Rust M,Kronenberger B.Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection[J].Am J Gastroenterol,2011,106(9):1663-9.
[15]Jiao X,Fan Z,Chen H,et al.Serum and exosomal miR-122 ans miR-199a as a biomarker to predict therapeutic efficacy of hepatitis C patients[J].J Med Virol.2017,89(9):1597-605.
[16]李毅,唐佩福.外泌体中Micro-RNA可作为疾病的生物标志物[J].中国组织工程研究,2016,20(51):7738-45.
[2]Cheng H R,Kao J H,Wu H L,et al.Clinical significance of circulating miR-122 in patients with dual chronic hepatitis B and Cvirus infection[J].Hepatol Int,2015,9(1):35-42.
[3]Longatti A.The dual role of exosomes in hepatitis A and C virus transmission and viral immune activation[J].Viruses,2015,7(12):6707-15.
[4]Zhang L,Zhang S,Yao J,et al.Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth[J].Nature,2015,527(7576):100-4.
[5]中华医学会肝病学分会.丙型肝炎防治指南(2015年版)[J].中华肝脏病杂志,2015,7(3):19-23.
[6]吴瑞珊,苏运钦,余广超,等.Taqman探针实时定量PCR检测肝脏疾病患者血清中miR-122的表达水平及其临床意义[J].中国病理生理杂志,2013,29(2):348-53.
[7]Thery C,Amigorena S,Raposo G,et al.Isolation and characterization of exosomes from cell culture supernatants and biological fluids[J].Curr Protoc Cell Biol,2006,3(22):21-3.
[8]Mitchell P S,Parkin R K,Kroh E M,et al.Circulating microR-NAs as stable blood-based markers for cancer detection[J].Proc Natl Acad Sci U S A,2008,105(30):10513-8.
[9]Chen X,Ba Y,Ma L,et al.Characterization of microRNAs in serum:a novel class of biomarkers for diagnosis of cancer and other diseases[J].Cell Res,2008,18(10):997-1006.
[10]Kosaka N,Iguchi H,Ochiya T.Circulating microRNA in body fluid:a new potential biomarker for cancer diagnosis and prognosis[J].Cancer Sci,2010,101(10):2087-92.
[11]Chang J,Nicolas E,Marks D,et al.miR-122,a mammalian liver-specific microRNA,is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1[J].RNA Biol,2004,1(2):106-13.
[12]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.
[13]张庆,刘杰,高晓红.HCV感染者中血清外泌体miRNA-122的检测及其临床意义[J].中华临床感染病杂志,2016,5(9):439-43.
[14]Bihrer V,Friedrich-Rust M,Kronenberger B.Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection[J].Am J Gastroenterol,2011,106(9):1663-9.
[15]Jiao X,Fan Z,Chen H,et al.Serum and exosomal miR-122 ans miR-199a as a biomarker to predict therapeutic efficacy of hepatitis C patients[J].J Med Virol.2017,89(9):1597-605.
[16]李毅,唐佩福.外泌体中Micro-RNA可作为疾病的生物标志物[J].中国组织工程研究,2016,20(51):7738-45.