摘要
目的探讨血浆microRNA-135a、microRNA-210在轻度认知损害患者中的诊断价值。方法收集于我院就诊的轻度认知损害患者及健康体检者的血液标本共80例,其中AMC组28例,VD-MCI 28例,AD-MCI 24例,采用RT-qPCR的方法进行血浆miRNA检测。结果 VD-MCI组血浆microRNA-135a为(4. 17×10~(-7)±8. 35×10~(-8)); AD-MCI组血浆microRNA-135a为(2. 83×10~(-7)±1. 72×10~(-7)); AMC组血浆microRNA-135a为(9. 87×10~(-7)±5. 66×10~(-7))。3组患者组间比较存在显著差异(F=30. 76,P=0. 00,P <0. 05)。VD-MCI组血浆microRNA-210为(4. 27×10~(-5)±1. 09×10~(-5)); AD-MCI组血浆microRNA-210为(6. 96×10~(-5)±2. 48×10~(-5)); AMC组血浆microRNA-210(1. 30×10~(-5)±7. 07×10~(-6))。3组患者组间比较存在显著差异(F=80. 43,P=0. 00,P <0. 05)。3组患者MMSE评分与两个检测指标间无明显相关性(P> 0. 05)。结论血浆microRNA-135a及microRNA-210检测可辅助诊断轻度认知功能损害,对AD-MCI诊断价值更大。
Objective To evaluate the clinical value of plasma microRNA-135 a,microRNA-210 in the detection of mild cognitive impairment. Methods The plasma samples of 80 subjects were collected from our hospital. There were 28 people with VD-MCI,24 people with AD-MCI and 28 age-matched control( AMC). RT-qPCR was applied to test the level of microRNA-135 a and microRNA-210. Results The levels of microRNA-135 a in plasma were( 4. 17 × 10~(-7)± 8. 35 ×10~(-8)),( 2. 83 × 10~(-7)± 1. 72 × 10~(-7)) and( 9. 87 × 10~(-7)± 5. 66 × 10~(-7)) in VD-MCI,AD-MCI and AMC. There were difference among three groups( F = 30. 76,P = 0. 00,P < 0. 05). The levels of microRNA-210 in plasma were( 4. 27 × 10~(-5)± 1. 09 × 10~(-5)),( 6. 96 × 10~(-5)± 2. 48 × 10~(-5)) and( 1. 30 × 10~(-5)± 7. 07 × 10~(-6)) in VD-MCI,AD-MCI and AMC. There were difference among three groups( F = 80. 43,P = 0. 00,P < 0. 05). There were no correlations between the MMSE score and the two biomarkers( P > 0. 05). Conclusions The plasma microRNA-135 a and microRNA 210 were potential biomarkers of MCI,especially for AD-MCI.
引文
[1]Bateman RJ,Xiong C,Benzinger T,et al.The dominantly inherited Alzheimer network clinical and biomarker changes in dominantly inherited Alzheimer’s disease[J].N Engl J Med,2012,367:795-804.
[2]Craig-Schapiro R,Fagan AM,Holtzman DM.Biomarkers of Alzheimer’s disease[J].Neurobiol Dis,2009,35,128-140.
[3]Fagan AM,Shaw LM,Xiong C,et al.Comparison of analytical platforms for cerebrospinal fluid measures ofβamyloid 1-42,total tau,and P-tau(181)for identifying Alzheimer disease amyloid plaque pathology[J].Arch Neurol,2011,68:1137-1144.
[4]De Meyer G,Shapiro F,Vanderstichele H,et al.Alzheimer’s disease neuroimaging initiative.diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people[J].Arch Neurol,2010,67:949-956.
[5]Mistur R,Mosconi L,Santi SD,et al.Current challenges for the early detection of Alzheimer’s disease:brain imaging and CSF studies[J].JClin Neurol,2009,5:153-166.
[6]Miller G.Alzheimer’s biomarker initiative hits its stride[J].Science,2009,326:386-389.
[7]Schmand B,Eikelenboom P,van Gool WA.Value of neurophysiological tests,neuroimaging,and biomarkers for diagnosing Alzheimer’s disease in younger and older age cohorts[J].J Am Geriatr Soc,2001,59:1705-1710.
[8]Ray S,Britschgi M,Herbert C,et al.Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins[J].Nat Med,2007,13:13591362.
[9]Reddy MM,Wilson R,Wilson J,et al.Identification of candidate Ig Gbiomarkers for Alzheimer’s disease via combinatorial library screening[J].Cell,2011,144:132-142.
[10]Nagele E,Han M,Demarshall C,et al.Diagnosis of Alzheimer’s disease based on disease-specific autoantibody profiles in human sera[J].PLo S One,2011,6:e23112.
[11]Ebert S,Sharp A.Roles for microRNAs in conferring robustness to biological processes[J].Cell,2012,149(3):515-524.
[12]Dong H,Li J,Huang L,et al.Serum MicroRNA serve as novel biomarker for the diagnosis of Alzheimer’s disease[J].Disease Markers,2015,2015(625659).
[13]Zhao Y,Alexandrov PN,Lukiw WJ.Anti-micro RNAs as novel therapeutic agents in the clinical management of Alzheimer’s disease[J].Frontiers in neuroscience,2016,10:59.
[14]Liu CG,Wang JL,Li L,et al.MicroRNA-384 regulates both amyloid precursor protein andβ-secretase expression and is a potential biomarkers for Alzheimer’s disease[J].Int J Mol Med,2014,34:160-166
[15]刘辰庚,孟双,张跃其,等.microRNA-135a在阿尔茨海默病患者中的检测价值[J].中国老年学杂志,2016,36(1):152-153.
[16]Paul P,Chakraborty A,Sarkar D,et al.Interplay between miRNAs and human diseases:a review[J].J Cell Physiol,2018,233:2007-2018.
[17]Rupaimoole R,Slack FJ.MicroRNA therapeutics:towards a new era for the management of cancer and other diseases[J].Nat Rev Drug Discov,2017,16:203-222.
[18]Ren CX,Leng RX,Fan YG,et al.MicroRNA-210 and its theranostic potential[J].Expert Opin Ther Target,2016,20:1325-1338.
[19]Zeng L,He X,Wang Y,et al.MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain[J].Gene Ther,2014,21:37-43.
[20]Ma Q,Dasgupta C,Li Y,et al.Inhibition of microRNA-210 provides neuroprotection in hypoxic-ischemic brain injury in neonatal rats[J].Neurobiol Dis,2016,89:202-212.
[21]Lou YL,Guo F,Liu F,et al.MiR-210 activates notch signaling pathway in angiogenesis induced by cerebral ischemia[J].Mol Cell Biochem,2012,370:45-51.