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急性缺血性中风患者循环中的miR-155与JAK2/STAT3轴及其与缺血后炎症和相关缺血性中风危险因素的关系

Circulating miR-155 and JAK2/STAT3 Axis in Acute Ischemic Stroke Patients and Its Relation to Post-Ischemic Inflammation and Associated Ischemic Stroke Risk Factors.

作者信息

Adly Sadik Noha, Ahmed Rashed Laila, Ahmed Abd-El Mawla Mai

机构信息

Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt.

Department of Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Int J Gen Med. 2021 Apr 21;14:1469-1484. doi: 10.2147/IJGM.S295939. eCollection 2021.

Abstract

BACKGROUND

"Micro RNAs and their target genes recently have been identified to play a crucial role in the molecular pathogenesis of post-stroke ischemic cellular injury, which elucidates their new role in ischemic stroke diagnosis and therapy". Thus, we evaluated the relative serum expression of miR-155, an inflammatory micro RNA, and the mRNAs (JAK2/STAT3) in acute ischemic stroke patients and its associations with the inflammatory cytokine TNF-α and different stroke risk factors.

SUBJECTS AND METHODS

The relative expression of serum miR-155 and mRNAs (JAK2/STAT3) was assessed using RT-PCR, serum TNF-α was measured using ELIZA in 46 acute ischemic stroke patients and 50 control subjects. Receiver operating characteristic (ROC) curve was constructed to assess the specificity and sensitivity of circulating miR-155, JAK2/STAT3 as biomarkers for acute ischemic stroke.

RESULTS

Circulating miR-155, JAK2/STAT3 were significantly up-regulated among stroke patients (8.5, 2.9, 4.2 fold respectively, <0.001) with significant increase in TNF-α (263.8 ± 10.7 pg/mL, <0.001). MiR-155, JAK2/STAT3 were positively correlated with TNF-α. MiR-155, JAK2/STAT3 were significantly increased in stroke patients and associated with risk factors such as hypertension, carotid atherosclerosis, and atrial fibrillation. Our study revealed that miR-155 has diagnostic accuracy for acute ischemic stroke where AUC=0.9, (<0.001).

CONCLUSION

The elevated expressions of circulating miR-155, JAK2/STAT3, and TNF-α in acute ischemic stroke patients could trigger post-stroke cellular inflammation. MiR-155 could be used as potential inflammatory biomarker for acute ischemic stroke. However, further clinical studies are still needed to determine the exact role of miRNAs and different signal transduction expressions in the stage of acute ischemic stroke.

摘要

背景

“最近已确定微小RNA及其靶基因在中风后缺血性细胞损伤的分子发病机制中起关键作用,这阐明了它们在缺血性中风诊断和治疗中的新作用”。因此,我们评估了急性缺血性中风患者中炎症性微小RNA miR-155及其mRNA(JAK2/STAT3)的相对血清表达,以及它们与炎症细胞因子TNF-α和不同中风危险因素的关联。

对象与方法

采用逆转录聚合酶链反应(RT-PCR)评估46例急性缺血性中风患者和50例对照者血清miR-155和mRNA(JAK2/STAT3)的相对表达,采用酶联免疫吸附测定(ELISA)检测血清TNF-α。构建受试者工作特征(ROC)曲线,以评估循环miR-155、JAK2/STAT3作为急性缺血性中风生物标志物的特异性和敏感性。

结果

中风患者中循环miR-155、JAK2/STAT3显著上调(分别为8.5倍、2.9倍、4.2倍,P<0.001),TNF-α显著升高(263.8±10.7 pg/mL,P<0.001)。miR-155、JAK2/STAT3与TNF-α呈正相关。中风患者中miR-155、JAK2/STAT3显著升高,并与高血压、颈动脉粥样硬化和心房颤动等危险因素相关。我们的研究表明,miR-155对急性缺血性中风具有诊断准确性,曲线下面积(AUC)=0.9,(P<0.001)。

结论

急性缺血性中风患者中循环miR-155、JAK2/STAT3和TNF-α表达升高可引发中风后细胞炎症。miR-155可作为急性缺血性中风潜在的炎症生物标志物。然而,仍需要进一步的临床研究来确定微小RNA和不同信号转导表达在急性缺血性中风阶段的确切作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f94/8071708/9a2a4fffe844/IJGM-14-1469-g0001.jpg

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