MiR-706 alleviates white matter injury via downregulating PKCα/MST1/NF-κB pathway after subarachnoid hemorrhage in mice
MiR-706 alleviates white matter injury via downregulating PKCα/MST1/NF-κB pathway after subarachnoid hemorrhage in mice
复制标题
MiR-706 通过下调 PKCα/MST1/NF-κB 通路减轻小鼠蛛网膜下腔出血后的白质损伤
DOI：
10.1016/j.expneurol.2021.113688
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发表时间：
2021-03-23
影响因子：
5.3
通讯作者：
Feng, Hua
中科院分区：
文献类型：
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作者：
Ru, Xufang;Qu, Jie;Feng, Hua
越来越多的自发性蛛网膜下腔出血（SAH）患者从手术和重症监护治疗中恢复，出院后仍存在认知功能障碍，这表明白色物质损伤在SAH急性期的重要性。本研究采用标准血管内穿孔法建立SAH小鼠模型，利用microRNA（miRNA）芯片分析SAH后白色组织基因表达的变化。结果显示，17种miRNA表达下调，包括miR-706、miR-669 a-5 p、miR-669 p-5 p、miR-7116- 5 p和miR-195 a-3 p; 13种miRNA表达上调，包括miR-6907- 5 p、miR-5135、miR-6982- 5 p、miR-668- 5 p和miR-8119。引人注目的是，miR-706显著下调，具有最高倍数变化。进一步的实验证实，miR-706可以减轻白色物质损伤并改善神经行为，至少部分是通过抑制PKC α/MST 1/NF-κ B通路和炎性细胞因子的释放。这些结果可能会为SAH后白色物质的病理生理过程提供更深入的了解，以及转化研究的潜在治疗策略。
Increasing numbers of patients with spontaneous subarachnoid hemorrhage(SAH) who recover from surgery and intensive care management still live with cognitive impairment after discharge, indicating the importance of white matter injury at the acute stage of SAH. In the present study, standard endovascular perforation was employed to establish an SAH mouse model, and a microRNA (miRNA) chip was used to analyze the changes in gene expression in white matter tissue after SAH. The data indicate that 17 miRNAs were downregulated, including miR-706, miR-669a-5p, miR-669p-5p, miR-7116-5p and miR-195a-3p, while 13 miRNAs were upregulated, including miR-6907-5p, miR-5135, miR-6982-5p, miR-668-5p, miR-8119. Strikingly, miR-706 was significantly downregulated with the highest fold change. Further experiments confirmed that miR-706 could alleviate white matter injury and improve neurological behavior, at least partially by inhibiting the PKC alpha/MST1/NF-kappa B pathway and the release of inflammatory cytokines. These results might provide a deeper understanding of the pathophysiological processes in white matter after SAH, as well as potential therapeutic strategies for the translational research.