加减薯蓣丸对轻、中度阿尔茨海默病患者血清特定microRNAs表达影响

谢文婷; 谭子虎; 陈延; 李贤炜; 柳弘汉

加减薯蓣丸对轻、中度阿尔茨海默病患者血清特定microRNAs表达影响

谢文婷¹,
谭子虎^2,3,,
陈延¹,
李贤炜^2,3,
柳弘汉^2,3

1.
湖北中医药大学中医临床学院，湖北武汉 430065
2.
湖北省中医院老年病科，湖北武汉 430061
3.
湖北省中医药研究院，湖北武汉 430074

计量
- 文章访问数: 2650
- HTML全文浏览量: 3
- PDF下载量: 1926
- 被引次数: 0
出版历程
- 收稿日期: 2018-05-06
- 刊出日期: 2018-09-10

Effect of Modified Yam Pills on Serum Specific MicroRNAs Expression in Patients with Mild and Moderate Alzheimer's Disease

XIEWen-ting¹,
TANZi-hu^{2,3
,},
CHENYan¹,
LIXian-wei^2,3,
LIUHong-han^2,3

1.
Clinical College of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China
2.
Geriatric Department, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China
3.
Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China

摘要

摘要: 目的探讨轻、中度阿尔茨海默病患者血清微小RNA（microRNA，miRNA）表达及加减薯蓣丸对其影响。方法检索Pubmed和中国知网数据库中研究AD患者外周血miRNAs文献，选择多篇（≥2篇）文献中一致性差异表达的miRNAs（至少1篇以血清为样本）作为目标miRNAs进行研究。56例轻、中度阿尔茨海默病患者给予加减薯蓣丸浓缩汤剂口服，每日2次，每次15 mL，疗程12周。另收集同期认知功能正常的老年健康体检者56例为对照组。采用荧光定量PCR法检测AD患者治疗前后及对照组血清目标miRNAs水平。结果与对照组比较，AD组治疗前血清miR-107、miR-29a、miR-29b、miR-181c、miR-125b、miR-135a、miR-342-3p表达明显降低，miR-146a表达明显升高（P<0.01）；与治疗前比较，AD组治疗后血清miR-107、miR-29a、miR-29b、miR-181c、miR-125b、miR-342-3p表达明显升高（P<0.05～0.01），miR-146a表达明显降低（P<0.01）。结论通过检测血清miR-107、miR-29a、miR-29b、miR-181c、miR-125b、miR-135a、miR-342-3p及miR-146a表达水平可能有助于AD患者早期诊断;加减薯蓣丸可能通过调节AD患者血清miR-107、miR-29a、miR-29b、miR-181c、miR-125b、miR-342-3p、miR-146a表达水平而发挥治疗AD的作用。
- 阿尔茨海默病 /
- microRNA /
- 早期诊断 /
- 治疗 /
- 加减薯蓣丸
Abstract: OBJECTIVE To explore the expression of serum microRNAs (miRNAs) in patients with mild and moderate Alzheimer's disease and the effect of modified Yam Pills on it. METHODS The literature of peripheral blood miRNAs in AD patients was retrieved in Pubmed and China National Knowledge Internet database. The miRNAs with consistent expression in multiple literatures were selected for the study. Totally 56 patients with mild and moderate Alzheimer's disease were treated with modified Yam Pills of 15 mL each time， twice a day for 12 weeks. Another 56 cases with normal cognitive function were collected as control group. The serum miRNAs levels of AD patients before and after treatment and control group were measured by fluorescence quantitative PCR. RESULTS Compared with the control group， the expression of serum miR-107， miR-29a， miR-29b， miR-181c， miR-125b， miR-135a and miR-342-3p were significantly decreased in the AD group， and the expression of miR-146a was significantly increased (P<0.01). Compared with those before treatment， the expression of serum miR-107， miR-29a， miR-29b， miR-181c， miR-125b and miR-342-3p were significantly increased after treatment in the AD group (P<0.05， P<0.01)， and the expression of miR-146a was significantly decreased (P<0.01). CONCLUSION Detecting the expression of serum miR-107， miR-29a， miR-29b， miR-181c， miR-125b， miR-135a， miR-342-3p and miR-146a may be helpful to the early diagnosis of AD patients. Modified Yam Pills may play a role in the treatment of AD by regulating the levels of serum miR-107， miR-29a， miR-29b， miR-181c， miR-125b， miR-342-3p and miR-146a in AD patients.
- Alzheimer's disease /
- microRNA /
- early diagnosis /
- treatment /
- modified Yam Pills

HTML全文

参考文献(53)

[1]	杨寰庆，王涛.阿尔茨海默病非编码RNA研究进展[J].国际检验医学杂志，2017，38(6):737-740.
[2]	虞桂，王阶.miRNA及其调控网络与中医治病求本机制研究[J].中华中医药杂志，2012，27(11):2789-2791.
[3]	田金洲.中国痴呆诊疗指南[M]. 北京:人民卫生出版社， 2012:328-333.
[4]	LEIDINGER P， BACKES C， DEUTSCHER S， et al. A blood based 12-miRNA signature of Alzheimer disease patients[J]. Genome Biol， 2013， 14(7): R78.
[5]	WANG T， CHEN K， LI H， et al. The feasibility of utilizing plasma miRNA107 and BACE1 messenger RNA gene expression for clinical diagnosis of amnestic mild cognitive impairment[J]. J Clin Psychiatry， 2015， 76(2): 135-141.
[6]	GEEKIYANAGE H， JICHA GA， NELSON PT， et al. Blood serum miRNA: non-invasive biomarkers for Alzheimer's disease[J]. Exp Neurol， 2012， 235(2): 491-496.
[7]	马腾.全血miR-29a/101作为阿尔茨海默病诊断性生物标志物的研究[D].青岛:青岛大学，2016.
[8]	VILLA C， RIDOLFI E， FENOGLIO C， et al. Expression of the transcription factor Sp1 and its regulatory hsa-miR-29b in peripheral blood mononuclear cells from patients with Alzheimer's disease[J]. J Alzheimers Dis， 2013， 35(3): 487-494.
[9]	TAN L， YU JT， LIU QY， et al. Circulating miR-125b as a biomarker of Alzheimer's disease[J]. J Neurol Sci， 2014， 336(1): 52-56.
[10]	KIKO T， NAKAGAWA K， TSUDUKI T， et al. MicroRNAs in plasma and cerebrospinal fluid as potential markers for Alzheimer's disease[J]. J Alzheimers Dis， 2014， 39(2): 253-259.
[11]	JIA LH， LIU YN. Downregulated serum miR-223 servers as biomarker in Alzheimer's disease[J]. Cell Biochem Funct， 2016， 34(4): 233-237.
[12]	KUMAR P， DEZSO Z， MACKENZIE C， et al. Circulating miRNA biomarkers for Alzheimer's disease[J]. PLoS ONE， 2013， 8(7): e69807.
[13]	TAN L， YU JT， TAN MS， et al. Genome-wide serum microRNA expression profiling identifies serum biomarkers for Alzheimer's disease[J]. J Alzheimers Dis， 2014， 40(4): 1017-1027.
[14]	黄雷.血清miRNA作为生物标志物诊断阿尔茨海默病[D].南京:南京大学，2012.
[15]	DONG H， LI J， HUANG L， et al. Serum microRNA profiles serve as novel biomarkers for the diagnosis of alzheimer's disease[J]. Dis Markers， 2015， 2015: 625659.
[16]	刘辰庚，王金玲，李蕾，等.阿尔茨海默病患者血液标本外吐小体中miRNA-135a的检测[J].现代生物医学进展，2013，13(22):4361-4363，4287.
[17]	项薇，高曲文，杨红军，等. miRNA-135a在阿尔茨海默病患者血液标本及PC-12细胞乏外吐小体中的变化及临床意义[J].广西医学，2014，36(6):715-717.
[18]	LIU C， WANG J， LI L， et al. MicroRNA-135a and-200b， potential biomarkers for Alzheimer's disease， regulate β secretase and amyloid precursor protein[J]. Brain Res， 2014， 1583: 55-64.
[19]	CHENG L， DOECKE JD， SHARPLES RA， et al. Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment[J]. Mol Psychiatry， 2015， 20(10): 1188-1196.
[20]	LUGLI G， COHEN AM， BENNETT DA， et al. Plasma exosomal miRNAs in persons with and without Alzheimer disease: altered expression and prospects for biomarkers[J]. PLoS ONE， 2015， 10(10): e0139233.
[21]	SCHIPPER HM， MAES OC， CHERTKOW HM， et al. MicroRNA expression in Alzheimer blood mononuclear cells[J]. Gene Regul Syst Biol， 2007， 1: 263-274.
[22]	VILLA C， FENOGLIO C， DE RIZ M， et al. Role of hnRNP-A1 and miR-590-3p in neuronal death: genetics and expression analysis in patients with Alzheimer disease and frontotemporal lobar degeneration[J]. Rejuvenation Res， 2011， 14(3): 275-281.
[23]	SHEINERMAN KS， TSIVINSKY VG， CRAWFORD F， et al. Plasma microRNA biomarkers for detection of mild cognitive impairment[J]. Aging (Albany NY)， 2012， 4(9): 590-605.
[24]	SHEINERMAN KS， TSIVINSKY VG， ABDULLAH L， et al. Plasma microRNA biomarkers for detection of mild cognitive impairment: biomarker validation study[J]. Aging (Albany NY)， 2013， 5(12): 925-938.
[25]	肖建廷，于杨，谭兰，等.阿尔茨海默病患者血清miR-9水平变化及意义[J]. 山东医药，2014，54(38):8-10.
[26]	LIU CG， SONG J， ZHANG YQ， et al. MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's disease[J].Mol Med Rep， 2014， 10(5): 2395-2400.
[27]	BHATNAGAR S， CHERTKOW H， SCHIPPER HM， et al. Increased microRNA-34c abundance in Alzheimer's disease circulating blood plasma[J]. Front Mol Neurosci， 2014， 7: 2.
[28]	LIU CG， WANG JL， LI L， et al. MicroRNA-384 regulates both amyloid precursor protein and β-secretase expression and is a potential biomarker for Alzheimer's disease[J]. Int J Mol Med， 2014， 34(1): 160-166.
[29]	BURGOS K， MALENICA I， METPALLY R， et al. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology[J]. PLoS ONE， 2014， 9(5): e94839.
[30]	XIE B， ZHOU H， ZHANG R， et al. Serum miR-206 and miR-132 as potential circulating biomarkers for mild cognitive impairment[J]. J Alzheimers Dis， 2015， 45(3): 721-731.
[31]	ZHU Y， LI C， SUN A， et al. Quantification of microRNA-210 in the cerebrospinal fluid and serum: Implications for Alzheimer's disease[J]. Exp Ther Med， 2015， 9(3): 1013-1017.
[32]	段冉冉，彭涛，李燕飞，等.阿尔茨海默病患者血浆microRNA-101a-3p的表达[J].中国老年学杂志，2015，35(16):4421-4423.
[33]	LI W， LI X， XIN X， et al. MicroRNA-613 regulates the expression of brain-derived neurotrophic factor in Alzheimer's disease[J]. Biosci Trends， 2016， 10(5): 372-377.
[34]	NAGARAJ S， LASKOWSKA-KASZUB K， DEBSKI KJ， et al. Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer's disease patients from non-demented subjects[J]. Oncotarget， 2017， 8(10): 16122.
[35]	曾庆宏，刘霞，庄爱霞，等.microRNA-107在阿尔茨海默病患者血清中的表达及临床意义[J].中国老年学杂志，2018，38(5):1156-1159.
[36]	WU Y， XU J， XU J， et al. Lower serum levels of miR-29c-3p and miR-19b-3p as biomarkers for Alzheimer's disease[J]. Tohoku J Exp Med， 2017， 242(2): 129-136.
[37]	KUMAR S， VIJAYAN M， REDDY PH. MicroRNA-455-3p as a potential peripheral biomarker for Alzheimer's disease[J]. Hum Mol Genet， 2017， 26(19): 3808-3822.
[38]	HARA N， KIKUCHI M， MIYASHITA A， et al. Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease[J]. Acta Neuropathol Commun， 2017， 5(1): 10.
[39]	LUKIW WJ， ZHAO Y， CUI JG. An NF-κB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells[J]. J Biol Chem， 2008， 283(46): 31315-31322.
[40]	WANG LL， HUANG Y， WANG G， et al. The potential role of microRNA-146 in Alzheimer's disease: biomarker or therapeutic target?[J]. Med Hypotheses， 2012， 78(3): 398-401.
[41]	KEATING SE， MALONEY GM， MORAN EM， et al. IRAK-2 participates in multiple Toll-like receptor signaling pathways to NFκB via activation of TRAF6 ubiquitination[J]. J Biol Chem， 2007， 282(46): 33435-33443.
[42]	LI YY， CUI JG， DUA P， et al. Differential expression of miRNA-146a-regulated inflammatory genes in human primary neural， astroglial and microglial cells[J]. Neurosci Lett， 2011， 499(2): 109-113.
[43]	JIAO Y， KONG L， YAO Y， et al. Osthole decreases beta amyloid levels through up-regulation of miR-107 in Alzheimer's disease[J]. Neuropharmacology， 2016， 108: 332-344.
[44]	AUGUSTIN R， ENDRES K， REINHARDT S， et al. Computational identification and experimental validation of microRNAs binding to the Alzheimer-related gene ADAM10[J]. BMC Med Genet， 2012， 13(1): 35.
[45]	MONCINI S， LUNGHI M， VALMADRE A， et al. The miR-15/107 family of microRNA genes regulates CDK5R1/p35 with implications for Alzheimer's disease pathogenesis[J]. Mol Neurobiol， 2017， 54(6): 4329-4342.
[46]	HEBERT SS， HORRE K， NICOLAI L， et al. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/β-secretase expression[J]. Proc Natl Acad Sci USA， 2008， 105(17): 6415-6420.
[47]	GEEKIYANAGE H， CHAN C. MicroRNA-137/181c regulates serine palmitoyltransferase and in turn amyloid β， novel targets in sporadic Alzheimer's disease[J]. J Neurosci， 2011， 31(41): 14820-14830.
[48]	赵娟娟，岳东旭，褚风云，等.微小RNAs在阿尔茨海默病Aβ沉积和Tau磷酸化中的作用[J].生命科学，2017，29(5):507-513.
[49]	BANZHAF-STRATHMANN J， BENITO E， MAY S， et al. MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer's disease[J]. EMBO J， 2014， 33(15): 1667-1680.
[50]	MICHELI F， PALERMO R， TALORA C， et al. Regulation of proapoptotic proteins Bak1 and p53 by miR-125b in an experimental model of Alzheimer's disease: Protective role of 17β-estradiol[J]. Neurosci Lett， 2016， 629: 234-240.
[51]	HU Z， YU D， GU Q， et al. miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression[J]. Nat Commun， 2014， 5: 3263.
[52]	JUNG YY， KIM KC， PARK MH， et al. Atherosclerosis is exacerbated by chitinase-3-like-1 in amyloid precursor protein transgenic mice[J]. Theranostics， 2018， 8(3): 749-766.
[53]	谭子虎，柳弘汉，潘海松，等.加减薯蓣丸治疗轻中度肾精亏虚证老年期痴呆的磁共振波谱研究[J].安徽中医药大学学报，2018，37(2):29-33.