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miRNA-34c-5p 对脑缺血/再灌注损伤起保护作用:涉及抗凋亡和抗炎作用。

MiRNA-34c-5p protects against cerebral ischemia/reperfusion injury: involvement of anti-apoptotic and anti-inflammatory activities.

机构信息

Trauma Center, Third Affiliated Hospital of Nanchang University, No. 739 Qingshan South Road, Nanchang City, Jiangxi Province, 330000, People's Republic of China.

出版信息

Metab Brain Dis. 2021 Aug;36(6):1341-1351. doi: 10.1007/s11011-021-00724-5. Epub 2021 Apr 12.

Abstract

MicroRNAs (miRNAs) are known as important regulators of gene expression and play important roles in diverse biological activities. However, the involvement of miRNAs in cerebral ischemia remains elusive. In the present study, using the middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reperfusion (OGD/RP)-induced cell injury model, we found that the expression levels of miR-34c-5p were significantly reduced in MCAO rats and OGD/RP cells. Overexpression of miR-34c-5p could improve the increased brain infarction, brain water content and neurological scores in MCAO rats, as well as the abnormal expression of inflammatory cytokines (TNF-α, IL-6, COX-2, iNOS, IL-10) in OGD/RP cells. Moreover, overexpression of miR-34c-5p was found to inhibit the activity of nuclear factor-kappa B (NF-κB) by regulating the expression of nuclear receptor coactivator 1 (NCOA1), and increase the apoptotic rate of cortical neurons by inhibiting the expression of Caspase-3 and Bax and upregulating the expression of Bcl-2. Taken together, our findings demonstrated that miR-34c-5p plays an important role in cerebral ischemia/reperfusion injury, which may be mediated through inflammatory and apoptotic signaling pathways.

摘要

微小 RNA(miRNAs)是已知的重要基因表达调控因子,在多种生物活性中发挥重要作用。然而,miRNAs 参与脑缺血的确切机制仍不清楚。本研究通过大脑中动脉闭塞(MCAO)模型和氧葡萄糖剥夺/再灌注(OGD/RP)诱导的细胞损伤模型发现,miR-34c-5p 的表达水平在 MCAO 大鼠和 OGD/RP 细胞中显著降低。miR-34c-5p 的过表达可改善 MCAO 大鼠的脑梗死、脑含水量和神经评分的增加,以及 OGD/RP 细胞中炎症细胞因子(TNF-α、IL-6、COX-2、iNOS、IL-10)的异常表达。此外,过表达 miR-34c-5p 被发现通过调节核受体共激活因子 1(NCOA1)的表达来抑制核因子-κB(NF-κB)的活性,并通过抑制 Caspase-3 和 Bax 的表达和上调 Bcl-2 的表达来增加皮质神经元的凋亡率。综上所述,我们的研究结果表明,miR-34c-5p 在脑缺血/再灌注损伤中发挥重要作用,其可能通过炎症和凋亡信号通路介导。

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