VEGF inhibits the inflammation in spinal cord injury through activation of autophagy.
VEGF inhibits the inflammation in spinal cord injury through activation of autophagy.
复制标题
VEGF 通过激活自噬抑制脊髓损伤中的炎症。
DOI：
10.1016/j.bbrc.2015.06.146
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Mei, Xifan
中科院分区：
文献类型：
--
作者：
Han, Donghe;Yuan, Yajiang;Bi, Jing;Mei, Xifan
血管内皮生长因子 (VEGF) 是一种分泌型有丝分裂原，与脊髓损伤 (SCI) 的血管生成和血管重建相关。长期以来，VEGF一直被认为是脊髓神经元存活的有效神经营养因子。然而，VEGF的神经保护机制仍不清楚。本研究旨在探讨VEGF对脊髓损伤的影响及其机制。对年轻雄性 Wistar 大鼠进行 SCI，然后在损伤后 24 小时将 VEGF165 直接注射到病变中心。我们通过尼氏染色检测了 Basso、Beattie 和 Bresnahan (BBB) 评分和运动神经元数量。通过Western blot和RT-PCR检测自噬相关蛋白Beclin1和LC3B的表达。我们还通过ELISA检测了LPS（脂多糖）处理的脊髓神经元-胶质细胞共培养物中炎症因子白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）和白细胞介素10（IL-10）的含量。我们发现给予 VEGF165 可以增加 SCI 引起的大鼠的 BBB 评分并减少运动神经元的损失。 VEGF降低大鼠IL-1β、TNF-α和IL-10蛋白表达，上调Beclin1和LC3B表达。在体外研究中，VEGF165 降低了 LPS 处理的脊髓神经元-胶质细胞共培养物培养基中 IL-1β、IL-10 和 TNF-a 的水平，而这种水平被自噬抑制剂 3-MA 部分阻断。此外，VEGF165上调共培养细胞中Beclin1和LC3B的表达。结果提示VEGF165通过抑制炎症、增强自噬功能减轻脊髓损伤。
Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis and re-vascularization of spinal cord injury (SCI). VEGF has long been thought to be a potent neurotrophic factor for the survival of spinal cord neuron. However, the neuroprotective mechanism of VEGF is still unclear. The aim of this study was to investigate the effect of VEGF on spinal cord injury and its mechanisms. Young male Wistar rats were subjected to SCI and then VEGF165were injected directly into the lesion epicenter 24 h post injury. We detected Basso, Beattie and Bresnahan (BBB) scores and numbers of motor neuron via Nissl staining. The expressions of autophagy related protein Beclin1 and LC3B were determined by Western blot and RT-PCR. We also detected the contents of inflammation factors interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-10(IL-10) in LPS (Lipopolysaccharide) treated spinal neuron-glia co-culture by ELISA. We found that VEGF165administration increased the BBB score and reduced the loss of motor neuron of rats induced by SCI. VEGF decreased the protein expressions of IL-1β, TNF-α and IL-10 and up-regulated the expressions of Beclin1 and LC3B of rats. In thein vitrostudy, VEGF165decreased the levels of IL-1β, IL-10 and TNF-a in the medium of LPS treated spinal neuron-glia co-culture, which was partially blocked by 3-MA, the inhibitor of autophagy. In addition, VEGF165up-regulate the expressions of Beclin1 and LC3B in co-culture cells. The results suggested that VEGF165attenuated the spinal cord injury by inhibiting the inflammation and increasing the autophagy function.
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影响因子：
3.3
作者：
J. Widenfalk;A. Lipson;Marie Jubran;C. Hofstetter;T. Ebendal;Yihai Cao;L. Olson
通讯作者：
J. Widenfalk;A. Lipson;Marie Jubran;C. Hofstetter;T. Ebendal;Yihai Cao;L. Olson
影响因子：
9.3
作者：
Sato A;Ohtaki H;Tsumuraya T;Song D;Ohara K;Asano M;Iwakura Y;Atsumi T;Shioda S
通讯作者：
Shioda S
影响因子：
16.2
作者：
Burda JE;Sofroniew MV
通讯作者：
Sofroniew MV
影响因子：
5.5
作者：
Du, Jianhai;Teng, Ru-Jeng;Shi, Yang
通讯作者：
Shi, Yang
影响因子：
4.6
作者：
Licht, Tamar;Eavri, Ronen;Keshet, Eli
通讯作者：
Keshet, Eli