Wen Lan, Liu Lei, Tong Linyan, Li Jinfang, Zhang Keming, Zhang Qinbin, Li Changqing
Department of Neurology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Neurology, First Affiliated Hospital of Chengdu Medical College, Chengdu 600000, China.
Genes Dis. 2019 Jan 17;6(4):448-454. doi: 10.1016/j.gendis.2019.01.001. eCollection 2019 Dec.
Cerebral ischemia is a major cause of mortality and long-term morbidity worldwide. NDRG4 has been shown to protect against cerebral ischemia, although the underlying mechanisms remain largely unclear. Here we found that NDRG4 expression was decreased in the brain tissues of ischemia/reperfusion (IR) rats, indicating increased apoptosis rates among cerebral cells. NDRG4 restoration via an adenovirus significantly attenuated cerebral infarct sizes and impairments in IR rats. Furthermore, adenovirus-mediated NDRG4 inhibited cell apoptosis in the brains of IR rats and regulated the expression of Bcl-2, Bax, caspase-3, and c-Fos. Moreover, we found that NDRG4 increased expression of BDNF, which is strongly related to cerebral ischemia and cellular apoptosis. Altogether, our findings demonstrate that NDRG4 protects cerebral IR injury by inhibiting cell apoptosis and regulates cerebral cell apoptosis by increasing BDNF expression. These results suggest that NDRG4 may be a therapeutic target for IR treatment.
脑缺血是全球范围内导致死亡和长期致残的主要原因。尽管其潜在机制仍不清楚，但已有研究表明NDRG4可预防脑缺血。在此我们发现，缺血/再灌注（IR）大鼠脑组织中NDRG4表达降低，提示脑细胞凋亡率增加。通过腺病毒恢复NDRG4可显著减小IR大鼠的脑梗死面积并减轻损伤。此外，腺病毒介导的NDRG4可抑制IR大鼠脑内细胞凋亡，并调节Bcl-2、Bax、caspase-3和c-Fos的表达。而且，我们发现NDRG4可增加BDNF的表达，而BDNF与脑缺血和细胞凋亡密切相关。总之，我们的研究结果表明，NDRG4通过抑制细胞凋亡来保护脑IR损伤，并通过增加BDNF表达来调节脑细胞凋亡。这些结果提示NDRG4可能是IR治疗的一个靶点。
