血管内皮生长因子与缺血性脑卒中的研究进展
摘要
<正>脑卒中包括缺血性脑卒中和出血性脑卒中,血管内皮生长因子(vascular endothelial growth factor,VEGF)是缺血性脑卒中的研究热点和潜在靶点。近年来发现,VEGF在缺血性脑卒中起重要作用。我们将探讨脑缺血诱导VEGF及其在缺血性脑卒中的病理生理作用,以及VEGF在缺血性脑卒中治疗方面的研究进展。1 VEGF概况VEGF是在血管发生和血管生成中扮演不同角色的强效生长因子。VEGF在肿瘤微血管通透性中作为促渗透因
引文
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[8]Reeson P,Tennant KA,Gerrow K,et al.Delayed inhibition of VEGF signaling after stroke attenuates blood-brain barrier breakdown and improves functional recovery in a comorbidity-dependent manner[J].J Neurosci,2015,35(13):5128-5143.DOI:10.1523/JNEUROSCI.2810-14.2015.
[9]Khan M,Dhammu TS,Matsuda F,et al.Promoting endothelial function by S-nitrosoglutathione through the HIF-1α/VEGF pathway stimulates neurorepair and functional recovery following experimental stroke in rats[J].Drug Des Devel Ther,2015,9:2233-2247.DOI:10.2147/DDDT.S77115.
[10]Jin K,Wang X,Xie L,et al.Transgenic ablation of doublecortin-expressing cells suppresses adult neurogenesis and worsens stroke outcome in mice[J].Proc Natl Acad Sci U S A,2010,107(17):7993-7998.DOI:10.1073/pnas.100015 4107.
[11]Bus P,Gerrits T,Heemskerk SAC,et al.Endoglin mediates vascular endothelial growth factor-A-induced endothelial cell activation by regulating Akt signaling[J].Am J Pathol,2018,188(12):2924-2935.DOI:10.1016/j.ajpath.2018.08.005.
[12]Hagberg CE,Falkevall A,Wang X,et al.Vascular endothelial growth factor B controls endothelial fatty acid uptake[J].Nature,2010,464(7290):917-921.DOI:10.1038/nature08945.
[13]Shim JW,Sandlund J,Madsen JR.VEGF:apotential target for hydrocephalus[J].Cell Tissue Res,2014,358(3):667-683.DOI:10.1007/s00441-014-1978-6.
[14]Del Bigio MR,Di Curzio DL.Nonsurgical therapy for hydrocephalus:a comprehensive and critical review[J].Fluids Barriers CNS,2016,13:3.DOI:10.1186/s12987-016-0025-2.
[15]Frezzetti D,Gallo M,Maiello MR,et al.VEGF as a potential target in lung cancer[J].Expert Opin Ther Targets,2017,21(10):959-966.DOI:10.1080/14728222.2017.1371137.
[16]Shim JW,Sandlund J,Hameed MQ,et al.Excess HB-EGF,which promotes VEGF signaling,leads to hydrocephalus[J].Sci Rep,2016,6:26794.DOI:10.1038/srep26794.
[17]Geiseler SJ,Morland C.The Janus face of VEGF in stroke[J].Int J Mol Sci,2018,19(5):E1362.DOI:10.3390/ijms19051362.
[18]Reeson P,Tennant KA,Gerrow K,et al.Delayed inhibition of VEGF signaling after stroke attenuates blood-brain barrier breakdown and improves functional recovery in a comorbiditydependent manner[J].J Neurosci,2015,35(13):5128-5143.DOI:10.1523/JNEUROSCI.2810-14.2015.
[19]Povysheva T,Shmarov M,Logunov D,et al.Post-spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG[J].J Neurosurg Spine,2017,27(1):105-115.DOI:10.3171/2016.9.SPINE15959.
[20]Tenenbaum L,Humbert-Claude M.Glial cell line-derived neurotrophic factor gene delivery in Parkinson's disease:a delicate balance between neuroprotection,trophic effects,and unwanted compensatory mechanisms[J].Front Neuroanat,2017,11:29.DOI:10.3389/fnana.2017.00029.
[2]Mackenzie F,Ruhrberg C.Diverse roles for VEGF-A in the nervous system[J].Development,2012,139(8):1371-1380.DOI:10.1242/dev.072348.
[3]Jean LeBlanc N,Guruswamy R,ElAli A.Vascular endothelial growth factor isoform-B stimulates neurovascular repair after ischemic stroke by promoting the function of pericytes via vascular endothelial growth factor receptor-1[J].Mol Neurobiol,2018,55(5):3611-3626.DOI:10.1007/s12035-017-0478-6.
[4]Chau MJ,Deveau TC,Song M,et al.iPSC transplantation increases regeneration and functional recovery after ischemic stroke in neonatal rats[J].Stem Cells,2014,32(12):3075-3087.DOI:10.1002/stem.1802.
[5]Wu CC,Wang LC,Su YT,et al.Syntheticα5β1integrin ligand PHSRN is proangiogenic and neuroprotective in cerebral ischemic stroke[J].Biomaterials,2018,185:142-154.DOI:10.1016/j.biomaterials.2018.09.014.
[6]Liu D,Ye Y,Xu L,et al.Icariin and mesenchymal stem cells synergistically promote angiogenesis and neurogenesis after cerebral ischemia via PI3Kand ERK1/2pathways[J].Biomed Pharmacother,2018,108:663-669.DOI:10.1016/j.biopha.2018.09.071.
[7]Du H,Li P,Pan Y,et al.Vascular endothelial growth factor signaling implicated in neuroprotective effects of placental growth factor in an in vitroischemic model[J].Brain Res,2010,1357:1-8.DOI:10.1016/j.brainres.2010.07.015.
[8]Reeson P,Tennant KA,Gerrow K,et al.Delayed inhibition of VEGF signaling after stroke attenuates blood-brain barrier breakdown and improves functional recovery in a comorbidity-dependent manner[J].J Neurosci,2015,35(13):5128-5143.DOI:10.1523/JNEUROSCI.2810-14.2015.
[9]Khan M,Dhammu TS,Matsuda F,et al.Promoting endothelial function by S-nitrosoglutathione through the HIF-1α/VEGF pathway stimulates neurorepair and functional recovery following experimental stroke in rats[J].Drug Des Devel Ther,2015,9:2233-2247.DOI:10.2147/DDDT.S77115.
[10]Jin K,Wang X,Xie L,et al.Transgenic ablation of doublecortin-expressing cells suppresses adult neurogenesis and worsens stroke outcome in mice[J].Proc Natl Acad Sci U S A,2010,107(17):7993-7998.DOI:10.1073/pnas.100015 4107.
[11]Bus P,Gerrits T,Heemskerk SAC,et al.Endoglin mediates vascular endothelial growth factor-A-induced endothelial cell activation by regulating Akt signaling[J].Am J Pathol,2018,188(12):2924-2935.DOI:10.1016/j.ajpath.2018.08.005.
[12]Hagberg CE,Falkevall A,Wang X,et al.Vascular endothelial growth factor B controls endothelial fatty acid uptake[J].Nature,2010,464(7290):917-921.DOI:10.1038/nature08945.
[13]Shim JW,Sandlund J,Madsen JR.VEGF:apotential target for hydrocephalus[J].Cell Tissue Res,2014,358(3):667-683.DOI:10.1007/s00441-014-1978-6.
[14]Del Bigio MR,Di Curzio DL.Nonsurgical therapy for hydrocephalus:a comprehensive and critical review[J].Fluids Barriers CNS,2016,13:3.DOI:10.1186/s12987-016-0025-2.
[15]Frezzetti D,Gallo M,Maiello MR,et al.VEGF as a potential target in lung cancer[J].Expert Opin Ther Targets,2017,21(10):959-966.DOI:10.1080/14728222.2017.1371137.
[16]Shim JW,Sandlund J,Hameed MQ,et al.Excess HB-EGF,which promotes VEGF signaling,leads to hydrocephalus[J].Sci Rep,2016,6:26794.DOI:10.1038/srep26794.
[17]Geiseler SJ,Morland C.The Janus face of VEGF in stroke[J].Int J Mol Sci,2018,19(5):E1362.DOI:10.3390/ijms19051362.
[18]Reeson P,Tennant KA,Gerrow K,et al.Delayed inhibition of VEGF signaling after stroke attenuates blood-brain barrier breakdown and improves functional recovery in a comorbiditydependent manner[J].J Neurosci,2015,35(13):5128-5143.DOI:10.1523/JNEUROSCI.2810-14.2015.
[19]Povysheva T,Shmarov M,Logunov D,et al.Post-spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG[J].J Neurosurg Spine,2017,27(1):105-115.DOI:10.3171/2016.9.SPINE15959.
[20]Tenenbaum L,Humbert-Claude M.Glial cell line-derived neurotrophic factor gene delivery in Parkinson's disease:a delicate balance between neuroprotection,trophic effects,and unwanted compensatory mechanisms[J].Front Neuroanat,2017,11:29.DOI:10.3389/fnana.2017.00029.