Xu Zheng, Han Kaiwei, Chen Jigang, Wang Chunhui, Dong Yan, Yu Mingkun, Bai Rulin, Huang Chenguang, Hou Lijun
Department of Neurosurgery in Chang Zheng Hospital, Neurosurgery Research Institution of Shanghai, Second Military Medical University, Shanghai, China.
J Neurochem. 2017 Sep;142(5):700-709. doi: 10.1111/jnc.14108. Epub 2017 Aug 16.
Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. VEGF has long been thought to be a potent neurotrophic factor for the survival of spinal cord neurons. However, the role of VEGF in the regulation of ischemic brain injury remains unclear. In this study, rats were subjected to MCAO (middle cerebral artery occlusion) followed by intraperitoneal injection of VEGF165 (10 mg/kg) immediately after surgery and once daily until the day 10. The expression of target genes was assayed using qPCR, western blot and immunofluorescence to investigate the role of VEGF165 in regulating ischemic brain injury. We found that VEGF165 significantly inhibited MCAO-induced up-regulation of Scavenger receptor class A (SR-A) on microglia in a VEGFR1-dependent manner. VEGF165 inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines IL-1β, tumor necrosis factor alpha (TNF-α) and iNOS in microglia. More importantly, the role of VEGF165 in inhibiting neuroinflammation is partially abolished by SR-A over-expression. SR-A further reduced the protective effect of VEGF165 in ischemic brain injury. These data suggest that VEGF165 suppresses neuroinflammation and ischemic brain injury by inhibiting SR-A expression, thus offering a new target for prevention of ischemic brain injury.
血管内皮生长因子（VEGF）是一种与血管生成相关的分泌型促有丝分裂原。长期以来，VEGF一直被认为是脊髓神经元存活的一种强效神经营养因子。然而，VEGF在缺血性脑损伤调节中的作用仍不清楚。在本研究中，大鼠接受大脑中动脉闭塞（MCAO）手术，术后立即腹腔注射VEGF165（10 mg/kg），每天一次，持续至第10天。使用定量聚合酶链反应（qPCR）、蛋白质免疫印迹法和免疫荧光法检测靶基因的表达，以研究VEGF165在调节缺血性脑损伤中的作用。我们发现，VEGF165以VEGFR1依赖的方式显著抑制MCAO诱导的小胶质细胞上清道夫受体A类（SR-A）的上调。VEGF165抑制脂多糖（LPS）诱导的小胶质细胞中促炎细胞因子白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和诱导型一氧化氮合酶（iNOS）的表达。更重要的是，SR-A的过表达部分消除了VEGF165在抑制神经炎症中的作用。SR-A进一步降低了VEGF165在缺血性脑损伤中的保护作用。这些数据表明，VEGF165通过抑制SR-A的表达来抑制神经炎症和缺血性脑损伤，从而为预防缺血性脑损伤提供了一个新的靶点。
