miR-18b attenuates cerebral ischemia/reperfusion injury through regulation of ANXA3 and PI3K/Akt signaling pathway
miR-18b attenuates cerebral ischemia/reperfusion injury through regulation of ANXA3 and PI3K/Akt signaling pathway
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DOI：
10.1016/j.brainresbull.2020.04.021
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发表时间：
2020-08-01
影响因子：
3.8
通讯作者：
Cao, Yi
中科院分区：
文献类型：
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作者：
Min, Xiao-li;He, Mu;Cao, Yi
近年来，研究表明miR-18b的紊乱与缺血性脑卒中有关。在这里，我们旨在研究miR-18b在脑缺血/再灌注（I/R）损伤中的潜在神经保护机制。建立体外氧糖剥夺/再灌注（OGDR）模型和体内大脑中动脉闭塞（MCAO）模型，模拟脑I/R损伤。本研究采用RT-PCR、western blotting、CCK-8、TUNEL、TTC染色等方法探讨miR-18b对脑I/R损伤的影响。结果显示，脑I/R损伤后miR-18b表达降低。此外，miR-18b在体外和体内均显示出对脑I/R损伤的神经保护作用，这些神经保护作用包括促进细胞活力，减少细胞凋亡，减少OGDR后SH-SY 5Y细胞炎症因子的产生，抑制mcao诱导的小鼠梗死面积、神经功能缺损和细胞凋亡。此外，miR-18b负调控ANXA3的表达，其对脑I/R损伤的神经保护作用被ANXA3推翻。此外，增加miR-18b或降低ANXA3可促进脑I/R损伤后sh - sy5y细胞中PI3K/Akt信号通路的激活。综上所述，这些数据表明miR-18b通过抑制ANXA3和激活PI3K/Akt通路来保护脑I/R损伤，为缺血性卒中治疗提供了一个有希望的治疗靶点。
Recent, research has displayed that the disorders of miR-18b are related to ischemic stroke. Here, we aimed to investigate the underlying neuroprotective mechanism of miR-18b in cerebral ischemia/reperfusion (I/R) injury. Oxygen-glucose deprivation/reperfusion (OGDR) model in vitro and middle cerebral artery occlusion (MCAO) model in vivo were established to simulate cerebral I/R injury. RT-PCR, western blotting, CCK-8, TUNEL, and TTC staining assays were applied in this study to explore the effect of miR-18b on cerebral I/R injury. Results displayed that miR-18b expression was reduced after cerebral I/R injury. Besides, miR-18b showed neuroprotective effects on cerebral I/R injury both in vitro and in vivo, These neuroprotective effects included promoting cell viability, decreasing cell apoptosis, reducing the production of inflammatory cytokines in SH-SY 5Y cells after OGDR and depressing MCAO-induced infarct size, neurological deficits and apoptotic cells in mice. Moreover, miR-18b negatively regulated ANXA3 expression, and its neuroprotection on cerebral I/R injury was overturned by ANXA3. Additionally, increasing miR-18b or decreasing ANXA3 promoted the activation of the PI3K/Akt signaling pathway in SH-SY 5Y cells after cerebral I/R injury. In conclusion, these data indicate that miR-18b protects against cerebral I/R injury by inhibiting ANXA3 and activating PI3K/Akt pathway, which provides a promising therapeutic target for ischemic stroke therapy.