Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Department of Neurology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
CNS Neurol Disord Drug Targets. 2023;22(1):137-147. doi: 10.2174/1871527321666220324115848.
Recent studies have uncovered that vitexin compound B-1 (VB-1) can protect neurons against hypoxia/reoxygenation (H/R)-induced oxidative injury through suppressing NOX4 expression.
The aims of this study are to investigate whether VB-1 can protect the rat brain against ischemia/ reperfusion (I/R) injury and whether its effect on NOX4 expression is related to modulation of certain miRNAs expression.
Rats were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score and infarct volume concomitant with an upregulation of NOX4 expression, increase in NOX activity, and downregulation of miR-92b.
Administration of VB-1 reduced I/R cerebral injury accompanied by a reverse in NOX4 and miR-92b expression. Similar results were achieved in a neuron H/R injury model. Next, we evaluated the association of miR-92b with NOX4 by its mimics in the H/R model. H/R treatment increased neurons apoptosis concomitant with an upregulation of NOX4 and NOX activity while downregulation of miR-92b. All these effects were reversed in the presence of miR-92b mimics, confirming the function of miR-92b in suppressing NOX4 expression.
We conclude the protective effect of VB-1 against rat cerebral I/R injury through a mechanism involving modulation of miR-92b/NOX4 pathway.
最近的研究发现,牡荆素化合物 B-1(VB-1)可以通过抑制 NOX4 表达来保护神经元免受缺氧/复氧(H/R)诱导的氧化损伤。
本研究旨在探讨 VB-1 是否可以保护大鼠大脑免受缺血/再灌注(I/R)损伤,以及其对 NOX4 表达的影响是否与某些 miRNAs 表达的调节有关。
大鼠进行 2 小时脑缺血,再灌注 24 小时,建立 I/R 损伤模型,模型显示神经功能缺损评分和梗死体积增加,NOX4 表达上调,NOX 活性增加,miR-92b 下调。
VB-1 减少 I/R 脑损伤,同时逆转 NOX4 和 miR-92b 表达。在神经元 H/R 损伤模型中也得到了类似的结果。接下来,我们通过 H/R 模型中的 miR-92b 模拟物评估了 miR-92b 与 NOX4 的相关性。H/R 处理增加了神经元凋亡,同时上调了 NOX4 和 NOX 活性,而下调了 miR-92b。在存在 miR-92b 模拟物的情况下,所有这些作用都得到了逆转,证实了 miR-92b 在抑制 NOX4 表达中的作用。
我们得出结论,VB-1 对大鼠脑 I/R 损伤的保护作用是通过调节 miR-92b/NOX4 通路来实现的。