中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (11): 2504-2511.doi: 10.4103/1673-5374.339009

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

沉默miRNA-324-3p对脑缺血的神经保护作用

  

  • 出版日期:2022-11-15 发布日期:2022-04-22
  • 基金资助:
    国家自然科学基金(81803937)、浙江省大学生科技创新活动计划(新苗人才计划)(2020R413079)、温州市科技计划项目(Y20210122)

Silencing miRNA-324-3p protects against cerebral ischemic injury via regulation of the GATA2/A1R axis

An-Qi Zhang1, #, Lu Wang1, #, Yi-Xiu Wang2, Shan-Shan Hong1, Yu-Shan Zhong1, Ru-Yi Yu1, Xin-Lu Wu1, Bing-Bing Zhou1, Qi-Min Yu1, Hai-Feng Fu1, Shuang-Dong Chen1, Yun-Chang Mo1, *, Qin-Xue Dai1, *, Jun-Lu Wang1, *   

  1. 1Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; 2Department of Anesthesiology, Wenzhou Central Hospital, Wenzhou, Zhejiang Province, China
  • Online:2022-11-15 Published:2022-04-22
  • Contact: Jun-Lu Wang, BS, wangjunlu973@163.com; Qin-Xue Dai, MD, daiqinxue@wzhospital.cn; Yun-Chang Mo, MD, myc1104@wmu.edu.cn.
  • Supported by:
    This study was funded by the National Natural Science Foundation of China, No. 81803937 (to YCM and QXD); Science and Technology Innovation Activity Plan for College Students of Zhejiang Province (Xinmiao Talent Plan), No. 2020R413079 (to AQZ); Wenzhou Science and Technology Plan Project, No. Y20210122 (to QXD).

摘要:

既往研究表明miR-324-3p与脑缺血的病理生理学改变有关,但其作用机制尚在进一步研究中。由此进行的体内体外及人体血液标本研究发现,miR-324-3p的表达水平在急性缺血性卒中(AIS)患者和缺血性卒中的体外和体内模型中都有所下降。体内实验发现miR-324-3p激动剂加剧了MCAO大鼠的缺血性脑损伤,使梗死体积和细胞凋亡增加,加重了神经功能的恶化。在原代大脑皮质神经元细胞和PC12细胞的体外OGD/REP模型中发现,miR-324-3p模拟物降低了抗凋亡BCL2蛋白水平和细胞活力,增加了促凋亡的BAX蛋白的水平和细胞凋亡,而miR-324-3p抑制剂则产生相反的效果。沉默miR-324-3p通过GATA2增加A1R表达。这些结果表明,沉默miR-324-3p通过GATA2/腺苷A1受体途径减轻缺血性脑损伤。

https://orcid.org/0000-0002-1525-3938 (Jun-Lu Wang); https://orcid.org/0000-0002-2516-5798 (Qin-Xue Dai); https://orcid.org/ 0000-0001-8671-6322 (Yun-Chang Mo)

Abstract: Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia, but the mechanism underlying this relationship is unclear. In this study, we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stroke. miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion, as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits. In a PC12 cell oxygen-glucose deprivation/reoxygenation model, a miR-324-3p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis, whereas treatment with a miR-324-3p inhibitor had the opposite effects. Silencing miR-324-3p increased adenosine A1 receptor (A1R) expression through regulation of GATA binding protein 2 (GATA2). These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.

Key words: acute ischemic stroke, adenosine A1 receptor, apoptosis, cerebral ischemia-reperfusion injury, cortical neurons, GATA2, middle cerebral artery occlusion, miR-324-3p, oxygen-glucose deprivation/reoxygenation, PC12 cells