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脑缺血再灌注后大鼠脑内 NDRG2 的时空表达。

Spatial-temporal expression of NDRG2 in rat brain after focal cerebral ischemia and reperfusion.

机构信息

Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.

出版信息

Brain Res. 2011 Mar 25;1382:252-8. doi: 10.1016/j.brainres.2011.01.023. Epub 2011 Jan 15.

Abstract

N-myc downstream regulated gene 2 (NDRG2) was reported to be widely expressed in the nervous system. However, the expression and potential role of NDRG2 in focal cerebral ischemia brain remain unclear. Herein, we investigated spatial-temporal expression of NDRG2 in the rat brain following transient focal cerebral ischemia. Male Sprague-Dawley rats underwent a 120-min transient occlusion of middle cerebral artery. Rats were killed and brain samples were harvested at 4, 12, 24, and 72h after reperfusion. Expression of NDRG2 in the brain was determined by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemical staining. Cellular apoptosis was assessed by TUNEL staining. The results showed that NDRG2 was expressed on cells with an astrocytes-like morphology in ischemic penumbra. NDRG2 mRNA and protein expression began to increase at 4h after reperfusion and peaked at 24h in the ischemic penumbra. By using immunofluorescence, NDRG2 signals were co-localized with GFAP-positive astrocytes, and NDRG2 expression in astrocytes translocated from a cytoplasm to a nuclear localization at 24h after reperfusion. Double immunofluorescent staining for TUNEL and NDRG2 showed that some NDRG2 signals co-localized with TUNEL-positive cells, and that the apoptotic cells increased with enhancement of NDRG2-positive signals. In conclusion, NDRG2 expression is up-regulated in ischemic penumbra following transient focal cerebral ischemia. NDRG2 expression in astrocytes may play important pathological roles in cell apoptosis after stroke.

摘要

N- 鼠类肉瘤滤过性毒菌致癌同源基因 2(NDRG2)广泛表达于神经系统中。然而,NDRG2 在局灶性脑缺血脑内的表达和潜在作用尚不清楚。在此,我们研究了短暂性大脑中动脉阻塞后大鼠脑内 NDRG2 的时空表达。雄性 Sprague-Dawley 大鼠接受 120 分钟的大脑中动脉短暂阻塞。再灌注后 4、12、24 和 72 小时处死大鼠并采集脑样本。采用逆转录聚合酶链反应(RT-PCR)、Western blot 分析和免疫组织化学染色检测脑内 NDRG2 的表达。采用 TUNEL 染色评估细胞凋亡。结果显示,缺血半影区内具有星形胶质细胞样形态的细胞表达 NDRG2。NDRG2 mRNA 和蛋白表达在再灌注 4 小时后开始增加,并在缺血半影区 24 小时时达到高峰。免疫荧光显示,NDRG2 信号与 GFAP 阳性星形胶质细胞共定位,NDRG2 表达在再灌注 24 小时后从细胞质转位到核定位。TUNEL 和 NDRG2 的双重免疫荧光染色显示,一些 NDRG2 信号与 TUNEL 阳性细胞共定位,且随着 NDRG2 阳性信号的增强,凋亡细胞增加。总之,短暂性大脑中动脉阻塞后缺血半影区内 NDRG2 的表达上调。星形胶质细胞中 NDRG2 的表达可能在中风后细胞凋亡中发挥重要的病理作用。

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