The First School of Clinical Medicine, Southern Medical University, Department of Anesthesiology, Southern Theater General Hospital of PLA.
Department of Anesthesiology, Southern Theater General Hospital of PLA, Guangzhou City, Guangdong Province, China.
Neuroreport. 2022 Mar 23;33(5):205-214. doi: 10.1097/WNR.0000000000001750.
The neuroprotective effect of dexmedetomidine (DEX) has been demonstrated in hypoxic-ischemic brain damage (HIBD) animal models, the mechanism of which will be the foothold in this work.
After establishment of HIBD rat model, the rats were treated with DEX, miR-20a-5p agomir and adenoviral methionine adenosyltransferase 2B (MAT2B) overexpression vector, and then their brain tissues were harvested. The infarction volume and pathological changes of these brain tissues were measured using the triphenyl tetrazolium chloride (TTC), Nissl and hematoxylin-eosin (HE) stainings. The levels of miR-20a-5p, Bcl-2, Bax and MAT2B in these brain tissues were detected by Real-Time PCR (RT-PCR) and western blot. The binding sites of MAT2B and miR-20a-5p were predicted using the TargetScan and verified using the dual-luciferase reporter assay. The memory deficits and spatial learning of rat pups were assessed by Morris water maze test.
MiR-20a-5p expression was upregulated, while MAT2B expression was downregulated in rats with HIBD. MAT2B was targeted by miR-20a-5p. DEX treatment improved the neurons and hippocampal tissue damage and decreased miR-20a-5p level in brain tissues of rats with HIBD. MiR-20a-5p overexpression overturned the protective effect of DEX on brain tissues and learning and memory abilities in rats with HIBD. Moreover, DEX promoted Bcl-2 level while inhibiting Bax level in HIBD rats' brain tissues. Besides, overexpressed MAT2B reversed the effect of overexpressed miR-20a-5p on the levels of MAT2B, Bcl-2 and Bax, brain tissue damage, as well as the learning and memory abilities in rats with HIBD.
DEX alleviated HIBD via the miR-20a-5p/MAT2B axis in rats.
右美托咪定（DEX）在缺氧缺血性脑损伤（HIBD）动物模型中表现出神经保护作用，其机制将成为本工作的立足点。
建立 HIBD 大鼠模型后，用 DEX、miR-20a-5p 激动剂和腺病毒蛋氨酸腺苷转移酶 2B（MAT2B）过表达载体处理大鼠，然后采集其脑组织。采用氯化三苯基四氮唑（TTC）、尼氏染色和苏木精-伊红（HE）染色测量这些脑组织的梗死体积和病理变化。通过实时 PCR（RT-PCR）和蛋白质印迹检测这些脑组织中 miR-20a-5p、Bcl-2、Bax 和 MAT2B 的水平。使用 TargetScan 预测 MAT2B 和 miR-20a-5p 的结合位点，并使用双荧光素酶报告基因检测进行验证。通过 Morris 水迷宫试验评估幼鼠的记忆缺陷和空间学习能力。
HIBD 大鼠中 miR-20a-5p 表达上调，MAT2B 表达下调。MAT2B 是 miR-20a-5p 的靶点。DEX 治疗改善了 HIBD 大鼠神经元和海马组织损伤，并降低了脑组织中 miR-20a-5p 的水平。过表达 miR-20a-5p 逆转了 DEX 对 HIBD 大鼠脑组织和学习记忆能力的保护作用。此外，DEX 促进了 HIBD 大鼠脑组织中 Bcl-2 水平的升高，同时抑制了 Bax 水平的升高。此外，过表达 MAT2B 逆转了过表达 miR-20a-5p 对 HIBD 大鼠脑组织中 MAT2B、Bcl-2 和 Bax 水平、脑组织损伤以及学习记忆能力的影响。
DEX 通过 miR-20a-5p/MAT2B 轴减轻 HIBD 大鼠的损伤。
