Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
J Cell Mol Med. 2020 Dec;24(24):14152-14159. doi: 10.1111/jcmm.16025. Epub 2020 Oct 29.
Stroke is a leading cause of death and disability, while its pathophysiological mechanisms are not fully understood. In this study, we used the tMCAO mice model to investigate the role of circCCDC9 in the pathogenesis of stroke. We found that the expression of circCCDC9 was significantly decreased in the brains of tMCAO mice. The Evens blue and brain water content were significantly higher in the Pre-IR and Pre-IR+Vector mice, while these patterns were partially reversed by overexpression of circCCDC9. The nitrite content and eNOS expression were decreased in the Pre-IR and Pre-IR+Vector groups, which was restored by circCCDC9 overexpression. Overexpression of circCCDC9 also inhibited the expression of Caspase-3, Bax/Bcl-2 ratio and the expression of Notch1, NICD and Hes1 in tMCAO mice. Knockdown of circCCDC9 increased the expression of Caspase-3, Bax/Bcl-2 ratio and the expression of Notch1, NICD and Hes1. In summary, overexpression of circCCDC9 protected the blood-brain barrier and inhibited apoptosis by suppressing the Notch1 signalling pathway, while knockdown of circCCDC9 had the opposite effects. Our findings showed that circCCDC9 is a potential novel therapeutic target for cerebrovascular protection in acute ischaemic stroke.
中风是死亡和残疾的主要原因，但其病理生理机制尚未完全阐明。在本研究中，我们使用 tMCAO 小鼠模型来研究 circCCDC9 在中风发病机制中的作用。我们发现，circCCDC9 的表达在 tMCAO 小鼠的大脑中显著降低。Pre-IR 和 Pre-IR+Vector 小鼠的伊文思蓝和脑含水量显著升高，而过表达 circCCDC9 则部分逆转了这种模式。Pre-IR 和 Pre-IR+Vector 组的亚硝酸盐含量和 eNOS 表达降低，而过表达 circCCDC9 则恢复了其表达。circCCDC9 的过表达还抑制了 tMCAO 小鼠中 Caspase-3、Bax/Bcl-2 比值以及 Notch1、NICD 和 Hes1 的表达。circCCDC9 的敲低增加了 Caspase-3、Bax/Bcl-2 比值以及 Notch1、NICD 和 Hes1 的表达。总之，circCCDC9 的过表达通过抑制 Notch1 信号通路来保护血脑屏障并抑制细胞凋亡，而 circCCDC9 的敲低则产生相反的效果。我们的研究结果表明，circCCDC9 是急性缺血性中风中脑血管保护的一个潜在的新型治疗靶点。
