Electroacupuncture Pretreatment Alleviates Cerebral Ischemia-reperfusion Injury by Down-regulating Mir-155-5p.

IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Current neurovascular research Pub Date : 2023-01-01 DOI:10.2174/1567202620666230828092916
Xuejing Li, Ying Wang, Xiang Zhou, Hui Wang, Jiang Xu
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Abstract

Background: Increasing evidence shows that electroacupuncture pretreatment (EP) plays a crucial role in cerebral ischemia-reperfusion (I/R) injury, and cerebral I/R injury is the most serious complication of ischemic stroke treatment. The role of miR-155-5p in cerebral I/R injury has been studied, but the regulation of EP on miR-155-5p has not been reported.

Methods: The middle cerebral artery occlusion (MCAO) mice were used to investigate the role of EP in cerebral I/R injury. Longa and modified neurological severity scores (mNSS) were used to evaluate neurological impairment. HE staining and TUNEL staining were used to evaluate brain injury. The expressions of miR-155-5p, Yin Yang 1 (YY1) and p53 were detected by qRT-PCR. The expressions of related proteins were detected by western blot. The binding of YY1 to miR- 155-5p was verified by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. Mice brain microvascular endothelial cells (BMECs) were isolated and cultured for in vitro experiments. Oxygen-glucose deprivation/reoxygenation (OGD/R) was used to verify the role of YY1, p53 and miR-155-5p in cerebral I/R injury in vitro.

Results: MCAO modeling induced brain injury, apoptosis, and increased levels of miR-155-5p, YY1, and p53. EP markedly alleviated brain injury and reduced levels of miR-155-5p, p53, and YY1. miR-155 agomir markedly increased the expression of miR-155-5p and p53. miR-155 antagomir decreased the levels of miR-155-5p and p53. Dual-luciferase reporter and ChIP assay verified that YY1 regulated miR-155-5p expression. YY1 shNRA greatly decreased miR-155-5p and p53. Inhibition of p53 decreased miR-155-5p expression. Both miR-155-5p inhibitor and YY1 shRNA promoted proliferation, inhibited apoptosis, and decreased levels of ICAM-1 and Eselectin of OGD/R-treated BMECs. Inhibition of p53 strengthened the effect of miR-155-5p inhibitor and YY1 shNRA on BMECs.

Conclusion: Electroacupuncture pretreatment alleviates cerebral ischemia-reperfusion injury by regulating the YY1/p53/miR-155-5p axis.

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电针预处理通过下调 Mir-155-5p 减轻脑缺血再灌注损伤
背景:越来越多的证据表明,电针预处理(EP)在脑缺血再灌注(I/R)损伤中起着至关重要的作用,而脑缺血再灌注损伤是缺血性脑卒中治疗中最严重的并发症。miR-155-5p在脑I/R损伤中的作用已有研究,但EP对miR-155-5p的调控作用尚未见报道:方法:采用大脑中动脉闭塞(MCAO)小鼠研究 EP 在脑 I/R 损伤中的作用。Longa 评分和改良神经系统严重程度评分(mNSS)用于评估神经系统损伤。HE 染色和 TUNEL 染色用于评估脑损伤。通过 qRT-PCR 检测 miR-155-5p、阴阳 1 (YY1) 和 p53 的表达。相关蛋白的表达通过 Western 印迹进行检测。通过双荧光素酶报告实验和染色质免疫沉淀(ChIP)实验验证了 YY1 与 miR- 155-5p 的结合。分离并培养小鼠脑微血管内皮细胞(BMECs)进行体外实验。结果表明:MCAO模型诱导了小鼠脑血管内皮细胞的损伤:结果:MCAO模型诱导了脑损伤、细胞凋亡以及miR-155-5p、YY1和p53水平的升高。miR-155 agomir能显著增加miR-155-5p和p53的表达,而miR-155 antagomir能降低miR-155-5p和p53的水平。双荧光素酶报告和 ChIP 检测验证了 YY1 调控 miR-155-5p 的表达。YY1 shNRA 大大降低了 miR-155-5p 和 p53 的表达。抑制 p53 会降低 miR-155-5p 的表达。miR-155-5p 抑制剂和 YY1 shRNA 都能促进 OGD/R 处理的 BMEC 的增殖、抑制凋亡并降低 ICAM-1 和 Eselectin 的水平。抑制 p53 可增强 miR-155-5p 抑制剂和 YY1 shNRA 对 BMECs 的作用:结论:电针通过调节YY1/p53/miR-155-5p轴缓解脑缺血再灌注损伤。
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来源期刊
Current neurovascular research
Current neurovascular research 医学-临床神经学
CiteScore
3.80
自引率
9.50%
发文量
54
审稿时长
3 months
期刊介绍: Current Neurovascular Research provides a cross platform for the publication of scientifically rigorous research that addresses disease mechanisms of both neuronal and vascular origins in neuroscience. The journal serves as an international forum publishing novel and original work as well as timely neuroscience research articles, full-length/mini reviews in the disciplines of cell developmental disorders, plasticity, and degeneration that bridges the gap between basic science research and clinical discovery. Current Neurovascular Research emphasizes the elucidation of disease mechanisms, both cellular and molecular, which can impact the development of unique therapeutic strategies for neuronal and vascular disorders.
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