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急性缺血性脑卒中患者阴阳证候淋巴细胞的独特 microRNAs 特征。

Unique MicroRNAs Signature of Lymphocyte of Yang and Yin Syndromes in Acute Ischemic Stroke Patients.

机构信息

Cerebrovascular Diseases Research Institute and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.

Beijing Geriatric Medical Research Center, Beijing, 100053, China.

出版信息

Chin J Integr Med. 2019 Aug;25(8):590-597. doi: 10.1007/s11655-018-2843-3. Epub 2018 Jun 20.

DOI:10.1007/s11655-018-2843-3
PMID:29926387
Abstract

OBJECTIVE

To identify the differentially expressed microRNAs (miRNAs) profiles of yang and yin syndromes in patients with acute ischemic stroke, and to provide the molecular basis of the classification of these two syndrome types in acute ischemic stroke patients.

METHODS

A microarray assay was performed to assess the expression pattern of miRNAs in the lymphocyte of acute ischemic stroke patients. Target genes for the deregulated miRNAs were predicated using the online bioinformatic algorithms and functional annotation via Kyoto encyclopedia of genes and genomes pathway analysis for miRNAs predicted targets was carried out. Based on the predicted target genes of differentially expressed miRNAs, the miRNA-gene-network and miRNA-pathway-network were constructed.

RESULTS

Yang score based on tongue texture, urine, dejecta, and appearance, etc. showed that clinical symptoms were distinct between yang and yin syndromes. There were significantly higher total leukocyte number and lower total protein level in patients with yang syndrome compared with those in patients with yin syndrome (P<0.05). Comprehensive miRNA analysis identified 36 unique down-regulated miRNAs in yang syndrome group, and 20 unique down-regulated and 2 unique up-regulated miRNAs in yin syndrome group. The key regulatory miRNAs, gene, and pathways in the yang syndrome were hsa-miR-93-5p and -320b, enabled homolog, the metabolic pathways and mitogen-activated protein kinase signaling pathways, respectively, while those in the yin syndrome were hsa-miR-424-5p and -106b-5p, CNOT4, hepatitis B and pathways in cancer, respectively.

CONCLUSION

These results offered insight into the molecular basis underlying the different pathogenesis of yang or yin syndrome, providing clues for the individualized therapeutic strategies of acute ischemic stroke.

摘要

目的

鉴定急性缺血性脑卒中患者阴阳两证差异表达的 microRNAs(miRNAs)谱,为急性缺血性脑卒中患者的这两种证型分类提供分子基础。

方法

采用微阵列分析评估急性缺血性脑卒中患者淋巴细胞中 miRNAs 的表达模式。利用在线生物信息学算法预测下调 miRNAs 的靶基因,并通过京都基因与基因组百科全书通路分析对 miRNA 预测靶基因进行功能注释。基于差异表达 miRNAs 的预测靶基因,构建 miRNA-基因网络和 miRNA 通路网络。

结果

基于舌象、尿液、粪便、外观等的 Yang 评分表明,阴阳两证的临床症状存在明显差异。与 yin 证组相比,yang 证组的总白细胞数明显较高,总蛋白水平明显较低(P<0.05)。综合 miRNA 分析鉴定出 yang 证组中 36 个独特下调的 miRNAs,yin 证组中 20 个独特下调和 2 个独特上调的 miRNAs。yang 证的关键调控 miRNAs、基因和通路分别为 hsa-miR-93-5p 和 -320b,同源物为代谢途径和丝裂原活化蛋白激酶信号通路;而 yin 证的关键调控 miRNAs、基因和通路分别为 hsa-miR-424-5p 和 -106b-5p、CNOT4、乙型肝炎和癌症通路。

结论

这些结果为阴阳两证不同发病机制的分子基础提供了深入了解,为急性缺血性脑卒中的个体化治疗策略提供了线索。

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