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浙江大学学报(医学版)  2022, Vol. 51 Issue (5): 634-639    DOI: 10.3724/zdxbyxb-2022-0224
细胞因子     
血小板衍生生长因子及其受体在脑出血中的作用
毛宝杰1,2,王明2,*(),万曙2,*()
1. 浙江中医药大学第二临床医学院,浙江 杭州 310053
2. 浙江大学医学院附属浙江医院脑科中心,浙江 杭州 310030
Platelet derived growth factor and its receptor in intracerebral hemorrhage
MAO Baojie1,2,WANG Ming2,*(),WAN Shu2,*()
1. The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China;
2. Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou 310030, China
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摘要:

脑出血是成人常见致死致残性神经系统疾病。血小板衍生生长因子(PDGF)信号通路对脑出血的发生发展起着重要作用。PDGF参与血管重塑,可以作为脑出血的主要病因之一脑淀粉样血管病的生物标志物;PDGF及其受体通过改变血脑屏障完整性及促进炎症反应参与脑出血后继发性损伤机制,还可能通过促进血管生成参与脑出血后的修复机制。本文综述了PDGF信号通路参与脑出血病理生理的最新研究进展,介绍了以PDGF受体为治疗靶点的相关拮抗剂,旨在为脑出血临床治疗方案提供依据。

关键词: 脑出血血小板衍生生长因子血小板衍生生长因子受体炎症血脑屏障综述    
Abstract:

Intracerebral hemorrhage (ICH) is a common and highly disabling or fatal neurological disorder in adults. Recent studies have suggested that the platelet derived growth factor (PDGF) signaling pathway plays an important role in the development of ICH. PDGF is involved in vascular remodeling and can be used as a biomarker of cerebral amyloid angiopathy which is one of the major causes of ICH. PDGF and its receptors are involved in the mechanism of the secondary injury after ICH by affecting the integrity of the blood-brain barrier and inflammatory response. PDGF and its receptors may also participate in the mechanism of repair after ICH by promoting angiogenesis. This article reviews the latest research progress on the involvement of PDGF signaling pathway in the pathophysiology of intracerebral hemorrhage, and introduces the relevant antagonists using PDGFR as the therapeutic target, to provide information for the development of therapeutic options for intracerebral hemorrhage.

Key words: Intracerebral hemorrhage    Platelet derived growth factor    Platelet derived growth factor receptor    Inflammation    Blood-brain barrier    Review
收稿日期: 2022-05-04 出版日期: 2022-12-28
CLC:  R43.34  
基金资助: 浙江省自然科学基金(Y21H090041);浙江省重点研发项目(2021C03105);浙江省医药卫生科技计划(WKJ-ZJ-2014)
通讯作者: 王明,万曙     E-mail: u
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引用本文:

毛宝杰,王明,万曙. 血小板衍生生长因子及其受体在脑出血中的作用[J]. 浙江大学学报(医学版), 2022, 51(5): 634-639.

MAO Baojie,WANG Ming,WAN Shu. Platelet derived growth factor and its receptor in intracerebral hemorrhage. J Zhejiang Univ (Med Sci), 2022, 51(5): 634-639.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0224        https://www.zjujournals.com/med/CN/Y2022/V51/I5/634

1 ANS J, KIMT J, YOONB W. Epidemiology, risk factors, and clinical features of intracerebral hemorrhage: an update[J]J Stroke, 2017, 19( 1): 3-10.
doi: 10.5853/jos.2016.00864
2 QURESHIA I, TUHRIMS, BRODERICKJ P, et al.Spontaneous intracerebral hemorrhage[J]N Engl J Med, 2001, 344( 19): 1450-1460.
doi: 10.1056/NEJM200105103441907
3 GROSSB A, JANKOWITZB T, FRIEDLANDERR M. Cerebral intraparenchymal hemorrhage[J]JAMA, 2019, 321( 13): 1295-1303.
doi: 10.1001/jama.2019.2413
4 SASAHARAM, FRIESJ W U, RAINESE W, et al.PDGF B-chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model[J]Cell, 1991, 64( 1): 217-227.
doi: 10.1016/0092-8674(91)90223-L
5 YANGP, MANAENKOA, XUF, et al.Role of PDGF-D and PDGFR-β in neuroinflammation in experimental ICH mice model[J]Exp Neurol, 2016, 157-164.
doi: 10.1016/j.expneurol.2016.06.010
6 HELDINC H, WESTERMARKB. Mechanism of action and in vivo role of platelet-derived growth factor[J]Physiol Rev, 1999, 79( 4): 1283-1316.
doi: 10.1152/physrev.1999.79.4.1283
7 REIGSTADL J, VARHAUGJ E, LILLEHAUGJ R. Structural and functional specificities of PDGF-C and PDGF-D, the novel members of the platelet-derived growth factors family[J]FEBS J, 2005, 272( 22): 5723-5741.
doi: 10.1111/j.1742-4658.2005.04989.x
8 SAKATAM, YANAMOTOH, HASHIMOTON, et al.Induction of infarct tolerance by platelet-derived growth factor against temporary focal ischemia[J]Brain Res, 1998, 784( 1-2): 250-255.
doi: 10.1016/S0006-8993(97)01345-0
9 TANGZ, ARJUNANP, LEEC, et al.Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation[J]J Exp Med, 2010, 207( 4): 867-880.
doi: 10.1084/jem.20091704
10 晋 军, 祝善俊, 祝之明, 等. 自发性高血压大鼠中血小板源生长因子-AA及其受体表达与血管平滑肌细胞增殖的关系[J]. 生理学报, 2002, 54(2): 145-148
JIN Jun, ZHU Shanjun, ZHU Zhiming, et al. Relationship between proliferation of vascular smooth muscle cells and PDGF-AA and PDGFR-α expression in SHRs[J]. Acta Physiologica Sinica, 2002, 54(2): 145-148. (in Chinese)
11 PARKERS B, DOBRIANA D, WADES S, et al.AT1 receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension[J]Am J Physiol-Heart Circ Physiol, 2000, 278( 2): H613-H622.
doi: 10.1152/ajpheart.2000.278.2.H613
12 吴娟娟, 倪 俊. 脑淀粉样血管病发病机制的研究进展 [J]. 中国卒中杂志, 2021, 16(12): 1278-1283
WU Juanjuan, NI Jun. Advances in the mechanism of cerebral amyloid angiopathy[J]. Chinese Journal of Stroke, 2021, 16(12): 1278-1283. (in Chinese)
13 SAKAIK, NOGUCHI-SHINOHARAM, IKEDAT, et al.Cerebrospinal fluid cytokines and metalloproteinases in cerebral amyloid angiopathy‐related inflammation[J]Acta Neurol Scand, 2021, 143( 4): 450-457.
doi: 10.1111/ane.13382
14 DASARIR, BONSACKF, SUKUMARI-RAMESHS. Brain injury and repair after intracerebral hemorrhage: The role of microglia and brain-infiltrating macrophages[J]Neurochem Int, 2021, 104923.
doi: 10.1016/j.neuint.2020.104923
15 LIZ, LIM, SHIS X, et al.Brain transforms natural killer cells that exacerbate brain edema after intracere-bral hemorrhage[J/OL]J Exp Med, 2020, 217( 12): e20200213.
doi: 10.1084/jem.20200213
16 KEEPR F, ZHOUN, XIANGJ, et al.Vascular disruption and blood-brain barrier dysfunction in intracerebral hemorrhage[J]Fluids Barriers CNS, 2014, 11( 1): 18.
doi: 10.1186/2045-8118-11-18
17 OBERMEIERB, DANEMANR, RANSOHOFFR M. Development, maintenance and disruption of the blood-brain barrier[J]Nat Med, 2013, 19( 12): 1584-1596.
doi: 10.1038/nm.3407
18 MAQ, HUANGB, KHATIBIN, et al.PDGFR-α inhibition preserves blood-brain barrier after intrace-rebral hemorrhage[J]Ann Neurol, 2011, 70( 6): 920-931.
doi: 10.1002/ana.22549
19 SUE J, FREDRIKSSONL, GEYERM, et al.Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke[J]Nat Med, 2008, 14( 7): 731-737.
doi: 10.1038/nm1787
20 SUE J, CAOC, FREDRIKSSONL, et al.Microglial-mediated PDGF-CC activation increases cerebrovascular permeability during ischemic stroke[J]Acta Neuropathol, 2017, 134( 4): 585-604.
doi: 10.1007/s00401-017-1749-z
21 LINDAHLP, JOHANSSONB R, LEVÉENP, et al.Pericyte loss and microaneurysm formation in PDGF-B-deficient mice[J]Science, 1997, 277( 5323): 242-245.
doi: 10.1126/science.277.5323.242
22 BHOWMICKS, D′MELLOV, CARUSOD, et al.Impairment of pericyte-endothelium crosstalk leads to blood-brain barrier dysfunction following traumatic brain injury[J]Exp Neurol, 2019, 260-270.
doi: 10.1016/j.expneurol.2019.03.014
23 MCDONALDO G, OWENSG K. Programming smooth muscle plasticity with chromatin dynamics[J]Circ Res, 2007, 100( 10): 1428-1441.
doi: 10.1161/01.RES.0000266448.30370.a0
24 YANGP, WUJ, MIAOL, et al.Platelet-derived growth factor receptor-β regulates vascular smooth muscle cell phenotypic transformation and neuroinflammation after intracerebral hemorrhage in mice[J/OL]Crit Care Med, 2016, 44( 6): e390-e402.
doi: 10.1097/CCM.0000000000001425
25 PARZYCHK R, KLIONSKYD J. An overview of autophagy: morphology, mechanism, and regulation[J]Antioxid Redox Signal, 2014, 20( 3): 460-473.
doi: 10.1089/ars.2013.5371
26 SALABEIJ K, CUMMINST D, SINGHM, et al.PDGF-mediated autophagy regulates vascular smooth muscle cell phenotype and resistance to oxidative stress[J]Biochem J, 2013, 451( 3): 375-388.
doi: 10.1042/BJ20121344
27 BAIY, CHENJ, SUNK, et al.A functional variant in promoter region of platelet-derived growth factor-D is probably associated with intracerebral hemorrhage[J]J Neuroinflammation, 2012, 9( 1): 26.
doi: 10.1186/1742-2094-9-26
28 韩 非, 王颖竹, 杨 鹏, 等. 血清PDGF-D表达水平与老年出血性脑卒中患者颅内血肿扩大的相关性[J]. 中国老年学杂志, 2020, 40(24): 5179-5182
HAN Fei, WANG Yingzhu, YANG Peng, et al. The correlation between the expression of PDGF-D in serum and the expansion of intracranial hematoma in elderly patients with hemorrhagic stroke[J]. Chinese Journal of Gerontology, 2020, 40(24): 5179-5182. (in Chinese)
29 裴 丹, 刘 学. 抑制PDGFRα活化对小鼠脑损伤后胶质细胞增殖和瘢痕形成的影响[J]. 吉林大学学报(医学版), 2020, 46(5): 1023-1028, I0005, I0006
PEI Dan, LIU Xue. Effect of inhibition of PDGFRα activation on glial cell proliferation and scar formation after brain injury in mice[J]. Journal of Jilin University (Medicine Edition), 2020, 46(5): 1023-1028, I0005, I0006. (in Chinese)
30 KANGM, YAOY. Oligodendrocytes in intracerebral hemorrhage[J]CNS Neurosci Ther, 2019, 25( 10): 1075-1084.
doi: 10.1111/cns.13193
31 JOSEPHM J E, CALIAPERUMALJ, SCHLICHTERL C. After intracerebral hemorrhage, oligodendrocyte precursors proliferate and differentiate inside white-matter tracts in the rat striatum[J]Transl Stroke Res, 2016, 7( 3): 192-208.
doi: 10.1007/s12975-015-0445-3
32 HUJ G, WUX J, FENGY F, et al.PDGF-AA and bFGF mediate B104CM-induced proliferation of oligodendrocyte precursor cells[J]Int J Mol Med, 2012, 30( 5): 1113-1118.
doi: 10.3892/ijmm.2012.1110
33 YAOZ F, WANGY, LINY H, et al.Transplantation of PDGF-AA-overexpressing oligodendrocyte precursor cells promotes recovery in rat following spinal cord injury[J]Front Cell Neurosci, 2017, 79.
doi: 10.3389/fncel.2017.00079
34 CALVERA R, HALLA C, YUW P, et al.Oligodendrocyte population dynamics and the role of PDGF in vivo[J]Neuron, 1998, 20( 5): 869-882.
doi: 10.1016/S0896-6273(00)80469-9
35 FRUTTIGERM, KARLSSONL, HALLA C, et al.Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice[J]Development, 1999, 126( 3): 457-467.
doi: 10.1242/dev.126.3.457
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