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腰椎间盘突出症患者非手术治疗前后外周血基因表达变化的特征及意义

[Characteristics and Significance of Gene Expression Changes in Peripheral Blood of Lumbar Disc Extrusion Patients before and after Nonoperative Treatment].

作者信息

Dai Guo-Gang, Wang Yi, Liao Shi-Chuan, Xia Jiao, Wang Feng, Huang Lei, Du Wan-Li, Tian Guo-Gang, Wen Jiang, Li Tao

机构信息

Department Ⅱ of Cervicodynia, Omalgia, Lumbago and Sciatica Department, Sichuan Provincial Orthopedics Hospital, Chengdu 610041, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2021 Sep;52(5):868-876. doi: 10.12182/20210960303.

DOI:10.12182/20210960303
PMID:34622608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10408881/
Abstract

OBJECTIVE

To define the gene expression characteristics in the peripheral blood of patients with lumbar disc extrusion (LDE) and the effect of nonoperative treatment on the gene expression.

METHODS

DNA microarray was used to identify semi-quantitatively the differentially expressed genes (DEGs) in the peripheral blood of patients with LDE and that of the healthy controls and the variation trend of these DEGs after nonoperative treatment. Enrichment analysis was done to reveal the functional characteristics of these DEGs, and network analysis was done to identify key genes that contribute to gene dysregulation. The levels of these key genes were measured by qRT-PCR to examine their expression in LDE patients and the controls, and the effect of nonoperative treatment on the expression level.

RESULTS

We identified 153 DEGs in the peripheral blood of LDE patients and healthy controls, including 131 upregulated genes and 22 downregulated genes. Enrichment analysis revealed that most of the DEGs were related to immunity and the inflammatory response. Network analysis revealed that toll-like receptor 4 ( 4 ), matrix metallopeptidase 9 ( 9) and myeloperoxidase ( ), cathelicidin antimicrobial peptide ( ), resistin ( ), toll-like receptor 5 ( 5) were the key genes in the protein-protein interaction network. These key genes were all enriched into the terms releated to immunity and the inflammatory response. The patients experienced pain relief after nonoperative treatment. Among the 153 DEGs, 5 , interleukin 1 receptor antagonist ( 1 ) and solute carrier family 8 member A1 ( 8 1) were downregulated after nonoperative treatment. qRT-PCR revealed that the levels of 4, 9 , , , , 5, 1 and 8 1 in the peripheral blood of the LDE patients were higher than those of the healthy control group ( <0.05). In addition, 5 1 and 8 1 expression levels decreased after treatmentin in comparison with the levels before treatment ( <0.05).

CONCLUSION

Gene expression in the peripheral blood of LDE patients was characterized by the dysregulation of immune and inflammatory response-related genes, among which, 4, 9, , , and 5, the genes relevant to immune and inflammatory response, played a key role in the dysregulation of gene expression in the peripheral blood of LDE patients. The outcome of non-operative treatment may be related to the downregulation of the overexpressed 5, 1 and 8 1 in the peripheral blood of patients.

摘要

目的

明确腰椎间盘突出症(LDE)患者外周血中的基因表达特征以及非手术治疗对基因表达的影响。

方法

采用DNA微阵列技术半定量鉴定LDE患者外周血与健康对照者外周血中差异表达基因(DEGs)以及非手术治疗后这些DEGs的变化趋势。进行富集分析以揭示这些DEGs的功能特征,并进行网络分析以确定导致基因失调的关键基因。通过qRT-PCR检测这些关键基因的水平,以检查它们在LDE患者和对照者中的表达情况以及非手术治疗对其表达水平的影响。

结果

我们在LDE患者和健康对照者的外周血中鉴定出153个DEGs,包括131个上调基因和22个下调基因。富集分析显示,大多数DEGs与免疫和炎症反应相关。网络分析显示,Toll样受体4(TLR4)、基质金属蛋白酶9(MMP9)、髓过氧化物酶(MPO)、cathelicidin抗菌肽(CAMP)、抵抗素(RETN)、Toll样受体5(TLR5)是蛋白质-蛋白质相互作用网络中的关键基因。这些关键基因均富集到与免疫和炎症反应相关的术语中。患者经非手术治疗后疼痛缓解。在这153个DEGs中,5、白细胞介素1受体拮抗剂(IL1RN)和溶质载体家族8成员A1(SLC8A1)在非手术治疗后下调。qRT-PCR显示,LDE患者外周血中TLR4、MMP9、MPO、CAMP、RETN、TLR5、IL1RN和SLC8A1的水平高于健康对照组(P<0.05)。此外,与治疗前水平相比,治疗后5、IL1RN和SLC8A1的表达水平降低(P<0.

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