miR-125b、miR-29a和miR-155-5p作为诊断结核性脑膜炎生物标志的研究
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摘要
目的探讨结核性脑膜炎患者脑脊液及血浆中micro RNA(mi R)-125b、mi R-29a和mi R-155-5p的表达水平及其临床意义。方法收集20例结核性脑膜炎患者(结脑组)和20例原发性头痛患者(对照组)的脑脊液和血浆,分别提取总RNA,使用实时定量PCR方法分别检测脑脊液和血浆中mi R-125b、mi R-29a及mi R-155-5p的表达水平。结果与对照组相比,结脑组脑脊液、血浆中mi R-29a、mi R-125b表达水平明显上调,结脑组血浆中mi R-155-5p表达水平明显上调,差异均有统计学意义(均P<0.01),而2组脑脊液中mi R-155-5p表达水平比较差异无统计学意义。结论 mi R-125b、mi R-29a和mi R-155-5p可能参与了调节结核性脑膜炎的发生、发展过程,mi R-125b和mi R-29a有可能作为潜在的诊断结核性脑膜炎的生物学标志。
Objective To investigate the expression levels of micro RNA(mi R)-125 b, mi R-29 a and mi R-155-5p in ce-rebrospinal fluid(CSF) and plasma from the patients with tuberculous meningitis and their clinic significance. Methods Cerebrospinal fluid and plasma samples were collected from 20 patients with tuberculous meningitis(tuberculous meningitisgroup) and 20 patients suffered from primary headache(control group). The total RNAs were extracted.The levels of mi R-125 b, mi R-29 a and mi R-155-5p were determined by real-time quantitative PCR(q-PCR). Results Levels of mi R-29 aand mi R-125 b in both CSF and plasma of patients in tuberculous meningitis group were significantly higher than those in pa-tients from control group with statistical significance(P<0.01). Mean time, the level of mi R-155-5p in plasma but not inCSF of patients in tuberculous meningitis group was higher than those in control group with statistical significance(P<0.01). Conclusion Expression of mi R-125 b, mi R-29 a and mi R-155-5p may participate in regulating the occurrence anddevelopment of tuberculous meningitis. And mi R-125 b and mi R-29 a may be used as potential biomarkers for diagnosing tu-berculous meningitis.
Objective To investigate the expression levels of micro RNA(mi R)-125 b, mi R-29 a and mi R-155-5p in ce-rebrospinal fluid(CSF) and plasma from the patients with tuberculous meningitis and their clinic significance. Methods Cerebrospinal fluid and plasma samples were collected from 20 patients with tuberculous meningitis(tuberculous meningitisgroup) and 20 patients suffered from primary headache(control group). The total RNAs were extracted.The levels of mi R-125 b, mi R-29 a and mi R-155-5p were determined by real-time quantitative PCR(q-PCR). Results Levels of mi R-29 aand mi R-125 b in both CSF and plasma of patients in tuberculous meningitis group were significantly higher than those in pa-tients from control group with statistical significance(P<0.01). Mean time, the level of mi R-155-5p in plasma but not inCSF of patients in tuberculous meningitis group was higher than those in control group with statistical significance(P<0.01). Conclusion Expression of mi R-125 b, mi R-29 a and mi R-155-5p may participate in regulating the occurrence anddevelopment of tuberculous meningitis. And mi R-125 b and mi R-29 a may be used as potential biomarkers for diagnosing tu-berculous meningitis.
引文
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[3]Fu Y,Yi Z,Wu X,et al.Circulating micro RNAs in patients with ac-tive pulmonary tuberculosisinfection[J].J Clin Microbiol,2011,49(12):4246-4251.doi:10.1128/JCM.05459-11.
[4]Yi Z,Fu Y,Ji R,et al.Altered micro RNA signatures in sputum of pa-tients with active pulmonary tuberculosis[J].PLo S One,2012,7(8):e43184.doi:10.1371/journal.pone.0043184.
[5]Wu J,Lu C,Diao N,et al.Analysis of micro RNA expression profilingidentifies mi R-155 and mi R-155*as potential diagnostic markersfor active tuberculosis:a preliminary study[J].Hum Immunol,2012,73(1):31-37.doi:10.1016/j.humimm.2011.10.003.
[6]Thwaites GE,van Toorn R,Schoeman J.Tuberculous meningitis:more questions,still too few answers[J].Lancet Neurol,2013,12(10):999-1010.doi:10.1016/S1474-4422(13)70168-6.
[7]Joosten AA,Van Der Valk P,Geelen JAG,et al.Tuberculous meningi-tis:pitfallsin diagnosis[J].Acta Neurol Scand,2000,102(6):388-394.doi:10.1034/j.1600-0404.2000.102006388.x.
[8]Creemers EE Tijsen AJ,Pinto YM.Circulating micro RNAs novelbiomarkers and extracellular communicators in cardiovascular dis-ease[J].Circ Res,2012,110(3):483-495.doi:10.1161/CIRCRESAHA.111.247452.
[9]Bartel DP.micro RNAs:genomics,biogenesis,mechanism and function[J].Cell,2004,116(2):281-297.doi:10.1016/S0092-8674(04)00045-5.
[10]Zhang YZ,Yi ZJ,Fu YR.Research progress on micro RNAs and pul-monary infection[J].Chin J Mol Immunol,2012,28(11):1223-1224.[张玉芝,伊正君,付玉荣.micro RNA与肺部感染的研究进展[J].细胞与分子免疫学杂志,2012,28(11):1223-1224].
[11]Singh PK,Singh AV,Chauhan DS.Current understanding on micro R-NAs and its regulation in response to mycobacterial infection[J].JBiomed Sci,2013,20(1):14.doi:10.1186/1423-0127-20-14.
[12]Brook M,Tchen CR,Santalucia T,et al.Posttranslational regulation oftristetraprolin subcellularlocalization and protein stability by p38mitogen-activated protein kinase and extracellular signalregulatedkinase pathways[J].Mol Cell Biol,2006,26(6):2408-2418.doi:10.1128/MCB.26.6.2408-2418.2006.
[13]Rajaram MVS,Ni B,Morris JD,et al.Mycobaterium tuberculosis lipo-mannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2(MK2)and micro RNA-125b[J].Proc NatlAcad,2011,108(42):17408-17413.doi:10.1073/pnas.1112660108.
[14]Ma F,Xu S,Liu X,et al.The micro RNA mi R-29 controls innate andadaptive immune responses to intracellular bacterial infection bytargeting interferon-γ[J].Nat Immunol,2011,12(9):861-869.doi:10.1038/ni.2073.
[15]Ghorpade DS,Leyland R,Kurowska-Stolarska M,et al.Micro RNA-155 is required for Mycobaterium bovis BCG-mediated apoptosis ofmarcrophages[J].Mol Cell Bio,2012,32(12):2239-2253.doi:10.1128/MCB.06597-11.