Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Incubation Center for Scientific and Technological Achievements, Kunming Medical University, Kunming, Yunnan, China.
Eur J Neurosci. 2022 Aug;56(3):4013-4030. doi: 10.1111/ejn.15720. Epub 2022 May 30.
Cerebral ischaemia reperfusion (CIR) affects microRNA (miR) expression and causes substantial inflammation. Here, we investigated the influence and underlying mechanism of miR-27a-3p in rats with CIR. First, biliverdin treatment relieved cerebral infarction and decreased the levels of serum interleukin (IL)-1β, IL-6, and TNF-α. Through our previous study, we found key miR-27a-3p and its targeted gene LITAF might involve in the molecular mechanism of CIR. Then, the regulation between miR-27a-3p and LITAF was verified by the temporal miR-27a-3p and LITAF expression profiles and luciferase assay. Moreover, intracerebroventricular injection of the miR-27a-3p mimic significantly decreased the LITAF, TLR4, NF-κB, and IL-6 levels at 24 h post-surgery, whereas miR-27a-3p inhibitor reversed these effects. Furthermore, miR-27a-3p mimic could relieve cerebral infarct and neurologic deficit after CIR. In addition, injection of miR-27a-3p mimic decreased neuronal damage induced by CIR. Taken together, our results suggest that miR-27a-3p protects against CIR by relieving inflammation, neuronal damage, and neurologic deficit via regulating LITAF and the TLR4/NF-κB pathway.
脑缺血再灌注（CIR）影响 microRNA（miR）表达并引起严重的炎症。在这里，我们研究了 miR-27a-3p 在 CIR 大鼠中的影响及其潜在机制。首先，胆红素处理减轻了脑梗死并降低了血清白细胞介素（IL）-1β、IL-6 和 TNF-α的水平。通过我们之前的研究，我们发现关键的 miR-27a-3p 及其靶向基因 LITAF 可能涉及 CIR 的分子机制。然后，通过时间 miR-27a-3p 和 LITAF 表达谱和荧光素酶测定验证了 miR-27a-3p 与 LITAF 之间的调节关系。此外，脑室内注射 miR-27a-3p 模拟物可显著降低手术后 24 小时的 LITAF、TLR4、NF-κB 和 IL-6 水平，而 miR-27a-3p 抑制剂则逆转了这些作用。此外，miR-27a-3p 模拟物可减轻 CIR 后的脑梗死和神经功能缺损。此外，注射 miR-27a-3p 模拟物可减轻 CIR 引起的神经元损伤。总之，我们的结果表明，miR-27a-3p 通过调节 LITAF 和 TLR4/NF-κB 通路减轻炎症、神经元损伤和神经功能缺损，从而对 CIR 起到保护作用。
