经鼻靶向中枢应用CGRP对SAH后CVS的缓解作用及对血管新生的促进作用
|
摘要
研究目的:
1、探讨CGRP经鼻给药后对SAH后CVS的缓解作用。
2、探讨经鼻应用CGRP对SAH后血管新生的影响和机制。
研究方法:
1、选用健康成年雄性Wister大鼠,采用枕大池二次注血法建立SAH模型,将动物随机分为正常对照组、SAH组、经鼻NS SAH组、经鼻CGRP SAH组。用体式显微镜及活体循环检测系统在第二次SAH 72h观察基底动脉(BA)管径;用激光多普勒血流计在第一次SAH制作前,第二次SAH鼻腔给药后1/2h,1h,6h,12h各测量一次顶叶皮层局部脑血流量(rCBF),对大鼠局部脑血流量进行动态观察。
2、建立大鼠SAH模型,将动物随机分为正常对照组、SAH组、经鼻NS SAH组、经鼻CGRP SAH组。于第二次SAH后72h,制备新鲜脑组织冠状冰冻切片,用荧光免疫组化法检测皮层和海马CD31的表达,用图像分析仪计数新生血管密度;用逆转录RT-PCR技术测定大脑皮层、海马等部位血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA表达;用West blot、免疫荧光法检测皮层和海马VEGF的表达。
研究结果:
1、各组动物第二次SAH后72h,SAH组和NS SAH组大鼠BA明显痉挛,管径缩窄严重,与正常对照组有显著性差异(P<0.01);CGRP SAH组大鼠BA轻微痉挛,管径挛缩不明显,与SAH组和NS SAH组有显著性差异(P<0.01)。各组大鼠BA管径分别为正常对照组的48.18%、47.69%、93.13%。第二次SAH后SAH组和NS SAH组,rCBF显著降低,与正常对照组有显著性差异(P<0.01);CGRP SAH组rCBF降低的程度小,与SAH组和NS SAH组有显著性差异(P<0.01)。各组在第二次SAH后rCBF降低,1 h下降至最低值,在12 h内无明显恢复趋势。
2、第二次SAH后72h,SAH组、经鼻NS SAH组与正常对照组比较皮层和海马CD31、VEGF表达增强,有较多阳性细胞(P<0.01);经鼻CGRP SAH组表达最强,有大量的免疫阳性细胞分部,与SAH组和NS SAH组有显著性差异(P<0.01)。SAH组和NS SAH组与正常对照组比较皮层和海马VEGF mRNA、VEGF蛋白表达增加(P<0.01);经鼻CGRP SAH组表达最强,与SAH组和NS SAH组有显著性差异(P<0.01)。
研究结论:
1、经鼻给予CGRP能缓解SAH后BA血管痉挛,增加顶叶皮层局部脑血流量(rCBF),改善SAH后脑循环,增加脑部血液供应,对SAH后CVS有缓解作用。
2、经鼻给予CGRP能促进大脑皮层和海马CD31表达,增加大脑皮层和海马VEGF mRNA及VEGF蛋白表达,增强VEGF分泌和释放,通过VEGF、CD31血管新生作用,促进SAH后血管生成,增加脑部血流量,改善脑循环,防治SAH后CVS。
OBJECTIVES:
1.To investigate the effect of CGRP given intranasally on relief CVS following SAH.
2.To investigate the effect and mechanism of CGRP given intranasally on new cerebral vessel generation after SAH.
METHOD:
1. In this study, adult male Wister rats were used as experimental animals. Cisterna injection twice of freshly autologous arterial blood was used to induce SAH in rats. The rats were divided into : normal control group, SAH group, per nasal NS SAH group, per nasal CGRP SAH group. Somatotype microscope and living body circulation measure system were used to observe the caliber of BA in 72h after second SAH ; To measure parietal cortex rCBF in before first SAH, in 1/2h, 1h, 6h, 12h after second SAH given intranasally by laser-Doppler flow meter, developmently observe regional cerebral blood floe of rats.
2. The SAH model in rats was established , the rats were divided into : normal control group, SAH group, per nasal NS SAH group, per nasal CGRP SAH group. Rats were sacrificed at 72h after second SAH, the brain were taken out and made into the coronal frozen section. Immunohistochemical staining was used to detect the expression of CD31 and VEGF in cortex and hippocamp respectively; the expression of VEGF mRNA and the protein expression of VEGF in cortex and hippocamp of brain were assessed by technic of TR-PCR and West blot respectively.
RESULT:
1.In 72h after second SAH, the BA in SAH group and NS SAH group obviously cramped, the caliber of BA was significantly coarctat compared with that in normal group (P<0.01); The BA in CGRP SAH group slighely cramped, the caliber of BA was lightly coarctat compared with that in SAH group and NS SAH group(P<0.01); the BA caliber of every group is 48.18% 47.69% 93.13% of normal group respectively. The rCBF in SAH group and NS SAH group was evidently degraged compared with normal group(P<0.01); the rCBF in CGRP SAH group was smally step down compared with SAH group and NS SAH group (P<0.01); The rCBF cut down after second SAH every group, nadir in 1h, did not obviously return within 12h.
2. In 72h after second SAH, the expression of CD31, VEGF enhance respectively in cortex and hippocamp in SAH group and NS SAH group that have more macs cell compared with normal group(P<0.01); the expression of CD31, VEGF in cortex and hippocamp in CGRP SAH group that abound with immue masculin cell is the most obvious contrasted to SAH group and NS SAH group (P<0.01); the expression of VEGF mRNA and the protein expression of VEGF in cortex and hippocamp in SAH group and NS SAH group increased respectively, cnotrast with that in normal group (P<0.01); the expression of VEGF mRNA and the protein expression of VEGF in cortex and hippocamp in CGRP SAH group was the most maximun respectively, cnotrast with that in SAH group and NS SAH group (P<0.01).
CONCLUSION:
1.The CGRP via intranasal pathway can relieve BA vasospasm after SAH, increase rCBF, improve cerebral circulation, raise brain blood provision, play an important role in releasing CVS following SAH.
2. The CGRP given intranaseny can stimulate CD31 expression in cortex and hippocamp, increase the density of new blood vessels, enhance the expression of VEGF cell VEGF mRNA VEGF protein, VEGF that can promote new blood generation is bloodvessel regulatory factor. Thus, the CGRP via intranasal pathway can promote new cerebral vessels generation, increase cerebral blood flow , improve cerebral circulation.
1、探讨CGRP经鼻给药后对SAH后CVS的缓解作用。
2、探讨经鼻应用CGRP对SAH后血管新生的影响和机制。
研究方法:
1、选用健康成年雄性Wister大鼠,采用枕大池二次注血法建立SAH模型,将动物随机分为正常对照组、SAH组、经鼻NS SAH组、经鼻CGRP SAH组。用体式显微镜及活体循环检测系统在第二次SAH 72h观察基底动脉(BA)管径;用激光多普勒血流计在第一次SAH制作前,第二次SAH鼻腔给药后1/2h,1h,6h,12h各测量一次顶叶皮层局部脑血流量(rCBF),对大鼠局部脑血流量进行动态观察。
2、建立大鼠SAH模型,将动物随机分为正常对照组、SAH组、经鼻NS SAH组、经鼻CGRP SAH组。于第二次SAH后72h,制备新鲜脑组织冠状冰冻切片,用荧光免疫组化法检测皮层和海马CD31的表达,用图像分析仪计数新生血管密度;用逆转录RT-PCR技术测定大脑皮层、海马等部位血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA表达;用West blot、免疫荧光法检测皮层和海马VEGF的表达。
研究结果:
1、各组动物第二次SAH后72h,SAH组和NS SAH组大鼠BA明显痉挛,管径缩窄严重,与正常对照组有显著性差异(P<0.01);CGRP SAH组大鼠BA轻微痉挛,管径挛缩不明显,与SAH组和NS SAH组有显著性差异(P<0.01)。各组大鼠BA管径分别为正常对照组的48.18%、47.69%、93.13%。第二次SAH后SAH组和NS SAH组,rCBF显著降低,与正常对照组有显著性差异(P<0.01);CGRP SAH组rCBF降低的程度小,与SAH组和NS SAH组有显著性差异(P<0.01)。各组在第二次SAH后rCBF降低,1 h下降至最低值,在12 h内无明显恢复趋势。
2、第二次SAH后72h,SAH组、经鼻NS SAH组与正常对照组比较皮层和海马CD31、VEGF表达增强,有较多阳性细胞(P<0.01);经鼻CGRP SAH组表达最强,有大量的免疫阳性细胞分部,与SAH组和NS SAH组有显著性差异(P<0.01)。SAH组和NS SAH组与正常对照组比较皮层和海马VEGF mRNA、VEGF蛋白表达增加(P<0.01);经鼻CGRP SAH组表达最强,与SAH组和NS SAH组有显著性差异(P<0.01)。
研究结论:
1、经鼻给予CGRP能缓解SAH后BA血管痉挛,增加顶叶皮层局部脑血流量(rCBF),改善SAH后脑循环,增加脑部血液供应,对SAH后CVS有缓解作用。
2、经鼻给予CGRP能促进大脑皮层和海马CD31表达,增加大脑皮层和海马VEGF mRNA及VEGF蛋白表达,增强VEGF分泌和释放,通过VEGF、CD31血管新生作用,促进SAH后血管生成,增加脑部血流量,改善脑循环,防治SAH后CVS。
OBJECTIVES:
1.To investigate the effect of CGRP given intranasally on relief CVS following SAH.
2.To investigate the effect and mechanism of CGRP given intranasally on new cerebral vessel generation after SAH.
METHOD:
1. In this study, adult male Wister rats were used as experimental animals. Cisterna injection twice of freshly autologous arterial blood was used to induce SAH in rats. The rats were divided into : normal control group, SAH group, per nasal NS SAH group, per nasal CGRP SAH group. Somatotype microscope and living body circulation measure system were used to observe the caliber of BA in 72h after second SAH ; To measure parietal cortex rCBF in before first SAH, in 1/2h, 1h, 6h, 12h after second SAH given intranasally by laser-Doppler flow meter, developmently observe regional cerebral blood floe of rats.
2. The SAH model in rats was established , the rats were divided into : normal control group, SAH group, per nasal NS SAH group, per nasal CGRP SAH group. Rats were sacrificed at 72h after second SAH, the brain were taken out and made into the coronal frozen section. Immunohistochemical staining was used to detect the expression of CD31 and VEGF in cortex and hippocamp respectively; the expression of VEGF mRNA and the protein expression of VEGF in cortex and hippocamp of brain were assessed by technic of TR-PCR and West blot respectively.
RESULT:
1.In 72h after second SAH, the BA in SAH group and NS SAH group obviously cramped, the caliber of BA was significantly coarctat compared with that in normal group (P<0.01); The BA in CGRP SAH group slighely cramped, the caliber of BA was lightly coarctat compared with that in SAH group and NS SAH group(P<0.01); the BA caliber of every group is 48.18% 47.69% 93.13% of normal group respectively. The rCBF in SAH group and NS SAH group was evidently degraged compared with normal group(P<0.01); the rCBF in CGRP SAH group was smally step down compared with SAH group and NS SAH group (P<0.01); The rCBF cut down after second SAH every group, nadir in 1h, did not obviously return within 12h.
2. In 72h after second SAH, the expression of CD31, VEGF enhance respectively in cortex and hippocamp in SAH group and NS SAH group that have more macs cell compared with normal group(P<0.01); the expression of CD31, VEGF in cortex and hippocamp in CGRP SAH group that abound with immue masculin cell is the most obvious contrasted to SAH group and NS SAH group (P<0.01); the expression of VEGF mRNA and the protein expression of VEGF in cortex and hippocamp in SAH group and NS SAH group increased respectively, cnotrast with that in normal group (P<0.01); the expression of VEGF mRNA and the protein expression of VEGF in cortex and hippocamp in CGRP SAH group was the most maximun respectively, cnotrast with that in SAH group and NS SAH group (P<0.01).
CONCLUSION:
1.The CGRP via intranasal pathway can relieve BA vasospasm after SAH, increase rCBF, improve cerebral circulation, raise brain blood provision, play an important role in releasing CVS following SAH.
2. The CGRP given intranaseny can stimulate CD31 expression in cortex and hippocamp, increase the density of new blood vessels, enhance the expression of VEGF cell VEGF mRNA VEGF protein, VEGF that can promote new blood generation is bloodvessel regulatory factor. Thus, the CGRP via intranasal pathway can promote new cerebral vessels generation, increase cerebral blood flow , improve cerebral circulation.
引文
[1] van Gijn J,Kerr RS,Rinkel GJ.Subarachnoid haemorrhage.Lancet,2007,369(9558):306-318
[2] Hansen-Schwartz J. Cerebral vasospasm: a consideration of the various cellular mechanisms involved in the pathophysiology.Neurocrit Care, 2004,1:235-246
[3] Crowley RW, Medel R, Kassell NF, el al. New insights intothe causes and therapy of cerebral vasospasm following sub-arachnoid hemorrhage. Drug Discov Today, 2008, 13 ( 5-6 ): 254-260
[4] Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev, 2004,84(3):903-934
[5] Yu XJ, Li CY, Wang KY, Dai HY. Calcitonin gene-related peptide regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes by activation of ERK1/2 MAPK. Regul Pept,2006,137(3):134-139
[6]邓水秀,秦旭平.降钙素基因相关肽的血管生物学功能多样性.国际病理科学与临床杂志,2006, 26(3):246-249
[7] Juul R, Edvinsson L, Jisrole S. Calcitonin gene-relat-ed peptide-LI in SAH in man signs of activation of thetrigemino cerebrovascular[J].Br J Neurosurg, 1990,4(3): 171-179
[8] Arienta C, Balbi S, Caroli M,et al. Depletion of cal-citonin gene-related peptide in perivascular never dur-ing acute phase of post-hemorrhagic vasospasm in therabbit[J].Brain Res Bull, 1991,27(5): 605-609
[9] Mathison S, Nagilla R, Kompella UB. Nasal route for direct delivery of solutes to the central nervous system: fact or fiction? J Drug Target,1998,5(6):415-441
[10]贾莉,孙保亮.中枢神经系统淋巴引流的研究进展.中国微循环, 2006,10(5): 377-380
[11] Nakayama T, Illoh K, Ruetzler C, Auh S, Sokoloff L, Hallenbeck J. Intranasal administration of E-selectin to induce immunological tolerization can suppress subarachnoid hemorrhage-induced vasospasm implicating immune and inflammatory mechanisms in its genesis. Brain Res, 2007, 1132(1):177-184
[12] Banks WA. The CNS as a target for peptides and peptide-based drugs. Expert Opin Drug Deliv,2006,3(6):707-712
[13]王峰,蒋新国.鼻勃膜作为脑内递药途径的研究进展. [J]药学学报,2001,36(8):636-640
[14] Vatter H, Weidauer S, Konczalla J, et al. Time course in the development of cerebral vasospasm after experimental subarachnoid hemorrhage: clinical and neuroradiologica assessment of therat double hemorrhage model [ J ]. Neurosurgery,2006,58(6):1190-1197
[15] Lu LF, Fiscus RR. Nitric oxide donors enhance calcitonin gene-re-lated peptide-induced elevations of cyclic AMP invascular smoothmuscle cells [J]. Eur J Pharmacol,1999,376(3):307-314
[16] Rosenblum WI, Shimizu T, Nelson GH. Endothelium-depend-ent effects of substance P and calcitonin gene-related peptide omouse pial arterioles [J]. Stroke,1993,24(7):1043-1047
[17] Holland JP, Sydserff SG, Taylor WS,et al. Calcitonin gene-re-lated peptide reduces brain injury in a rat model of focal cere-bral ischemia [J]. Stroke,1994,25(10):2055-2059
[18]武晓玉,高永良经鼻私膜递送人脑给药途径的研究进展「J」中国药学杂志,2003,38(8):561一564
[19] IllumL Transporoofdrogsfron henasalcavitytoth entra-nervousSystem「JEu:JPhar,Sci,2000,11(1):1一18
[20] Roux S,et al.The role of endothelin cerebral vasospasm[J].Neurosurgery.1995:37-78
[21]安蔚,孙保亮,杨明峰..经斜坡法大鼠基底动脉在体观测方法的建立[J]泰山医学院学报,2005,26:278-280
[22] Sun BL, Zhang SM, Xia ZL, et a.l The effects ofnimodip-ine on regional cerebralblood flow, brainwater and electro-lytes contents in rats with subarachnoid hemorrhage[ J].ClinHemorheoMicrocirc, 2003, 29(3,4): 337-344
[23] MEGURO T,CLOWER B R,CARPENTER R,et al.Im-proved rat model for cerebralvasospasm studies[J].Neurol Res,2001,23(7):761-766
[24] PRUNELL G F,MATHIESEN T,SVENDGAARD N A.Anew experimental model in rats for study of the pathophy-siology of subarachnoid hemorrhage[J].Neuroreport,2002,13(18):2553-2556
[25] PRUNELL G F ,MATHIESEN T ,DIEMER N H ,et al .Experimental subarachnoidhemorrhage:subarachnoid blood volume,mortality rate,neuronal death,cerebral blood flow , and perfusion pressure in three different rat models[J]. Neurosurgery,2003,52(1):165-176
[26] Gules I,Satoh M,Clower BR,et al.Comparison of three ratmodels of cerebral vasospasm[J].Am J Physiol Heart CircPhysiol,2002;283(6):2551-2559
[27] Meguro T,Clower BR,Carpenter R,et al.Improved rat model for cerebral vasospasm studies[J].Neurol Res,2001;23(7):761-766
[28] Suzuki H,Kanamaru K,Tsunoda H,et al.Heme oxyge-nase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats[J].J Clin Invest,1999;104(1):59-66
[29]Harada S,Kamiya K,Masago A,et al.Subarachnoid hemor-rhage induces c-fos,c-jun and hsp70 mRNA expression in rat brain[J].Neuroreport,1997;8(15):3399-3404
[30]武晓玉,高永良经鼻私膜递送人脑给药途径的研究进展「J」中国药学杂志,2003,38(8):561一564
[31]朱长庚,神经解剖学[M]北京:人民卫生出版社,2002.838-839
[32]相小强,陶涛,陈庆华.透血脑屏障制剂的研究进展[J].中国新药杂志,2002,11(7):519
[33] ILLUM L·Nasal drug delivery-possibilities, problems and solutions[J]·J Controlled Release, 2003, 87(1-3): 187-198
[34] Juul R, Edvinsson L, Jisrole SE. Calcitonin gene-related peptide-LI in SAH in man signs of activation of the trigeminal cerebrovascbular. Br J Nearosurg,1990,4(3):171
[35] Arienta C,Balli S,Caroli M,et al. Depletion of calcitonin gene-related peptide in perivascular nerve during acute phase of posthemorrhagic vasospasm in the rabbit. Brain Res Bull,1991,27:605
[36] Edvinsson L, Ekman R, Jansen I, et a.l Reduced levels of calci-tonin gene - related peptide - like immunoreactivity in human brain vessels after subarachnoid haemorrhage[J]. Neurosci Lett,1991, 121: 151-154
[37] Pluta RM, Dejam A, GrimesG, eta.l Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage[J]. JAMA, 2005,293(12): 1477-1484
[38] DeHoon JN,Pickkers P,Smits P,et al.Calcitonin gene-related pep-tide:Exploring its vasodilatingmechanism of action in humans[J].Clin Pharmacol Ther,2003,73(4):312-321
[39] SatohM,Perkins E,Kimura H,et al.Posttreatment with adenovirus-mediated gene transfer of calcitonin gene-related peptide reverse cere-bral vasospasm in dogs[J].J Neurosurg,2002,97(1):136-142
[40]王轩,张颜波,孙保亮,等.蛛网膜下腔出血后脑血管痉挛分子机制的研究进展[J].中国微循环,2007,11(3):216-218
[41]邓水秀,秦旭平.降钙素基因相关肽的血管生物学功能多样性[J].国际病理科学与临床杂志,2006,26(3):246-249.
[42]王德超,申文增,史树堂,等.大鼠弥漫性脑损伤后脑组织中MDA和SOD的变化[J].河北职工医学院学报,2005,22(4):1-2
[43]叶季鲜,李红梅,黄静,等.降钙素基因相关肽对血管升压素缩血管效应的影响[J].心脏杂志,2003,15(6):493-494
[44] Hendryk S,Jarzab B,Josko J.Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH[J].Neuro Endocrinol Lett.2004,25:141-147
[45] Fassbender K,Hodapp B,Rossol S,et al.Inflammatory cytokines in subarachnoid hemorrhage:association with abnormal blood flow velocities in basal cerebral arteries[J].J Neurol Neurosurg Psychiatry.2001,70:534–537
[46] Kaynar MY,Tanriverdi T,Kafadar AM,et al.Detection of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in both cerebrospinal fluidand serun of patients after aneurysmal subarachnoid hemorrhage[J].J Neurosurg.2004,101:1030-1036
[47]张晓钰,周东.降钙素基因相关肽对中枢神经系统的影响[J].国外医学神经病学神经外科学分册.2005,32(2):134-137
[48] ButtE,BernhardtM,SmolenskiA,et al.Endothelial nitric-oxide synthase (typeⅢ) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases[J].J BiolChem,,2000,,275:5179-5187
[49]Dietrich HH , Dacey CG . Molecular key to the problem of cerebralvasospasm.Neurosurgery[J]. 2000,46(3):517-530
[50] Gilbert P,Tremblay J,Thorin E.Endothelium-detrived endothelin-1 reduces cerebral artery sensitivity to nitric oxide by a protein kinase C independent pathway[J].Stroke.2001,32(10):2351-2355
[51] Brain SD,Grant AD.Vascular actions of calcitonin gene-related peptide and adrenomedullin[J].Physiol Rev,2004,84(3):903-934
[52]林平,赵守琪,刘洋,等.CGRP对葡萄糖诱导血管内皮细胞凋亡保护作用的研究[J].哈尔滨医科大学学报,2005,39(2):118-120
[53] Schoch B, Regel JP, W ichertM,el al.Analysis of intrathe-cal interleukin-6 as a potential predictive factor for vasospasm in subarachnoid hemorrhage. Neurosurgery, 2007, 60 ( 5 ):828-836
[54] ChristopherG,HarrodMS, Bemard R, et al. Prediction of cerebral vasospasm in patients presenting with aneurymal subarachnoid hemorrhage: a review. Neurosurg, 2005, 56 ( 4 ): 633-652
[55] GreenbergMS·Handbook ofNeurosurg[M]·NewYork: ThiemeMedicalpublish, 2000
[56] Zhang JH·Progress in reuroscience [M ]. BeiJing: Higher EducationPress, 2004
[57] Hoh BL,TopcuogluMA, SinghalAB, etal·Effectofclipping,Craniotomy,or intravascular coiling on cerebral vasospasm and patient outcome after aneurismal subarachnoid hemorrhage[ J]·Neurosurg, 2004, 55(4): 779-786
[59] Dorsch AD, NicholasWC·Therpeutic approaches to vasospasm in subarachnoid hemorrhage·Current Opinion in Critical[ J]·Care, 2002, 8(2): 128-133
[1] Maruotti N, Cantatore FP, Crivellato E,et al. Angiogenesis inrheumatoid arthritis[J]. HistolHistopatho,l 2006, 21(5): 557-566
[2]刘文韬,陈国玉,夏建国,等.胃癌微卫星不稳定性与血管内皮生长因子表达关系的研究[J].医学研究生学报, 2007, 18(2): 37-40
[3]高媛,高建忠,孙启鸿.血小板内皮细胞黏附分子1(PECAM-1)的研究[J].细胞与分子免疫学杂志, 2005, 21(3): 40-42
[4] Thompson RD, WakelinMW, LarbiKY,et al. Divergent effects of platelet-endothelial cell adhesion molecule-1 and 3 integrin blockade on leukocyte transmigrationin vivo[J].J Immunol, 2000, 165(1):426-434
[5] CaoG, O’Brien CD, Zhou Z,etal. Involvementofhuman PECAM-1 in angiogenesis andin vitroendothelial cellmigration[J].PhysiolCellPhysiol, 2002, 282(5):C1181-C1190
[6] Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases[J].Nature, 2000, 407(6801): 249-257
[7] NeufeldqCohenT,GengrinovitehS,etal.Vascularendothelial growthfactor(VEGF)anditsrecePtors.FasebJJan1999;13(1):9一22
[8] Rossler J, Lagodny J. Blood and lymph vessels in embryonic tumors. Hematol Oncol, 2005, 23 (3-4): 94-101
[9] Carmeliet P. Angiogenesis in life, disease and medicine.Nature, 2005, 438 (7070): 932-936
[10] SiemeisterG, SehnurrB, MohrsK, eta.l Expression ofbiologically active isoforms of the tumor angiogenesis factor VEGF in Escherichia coli[J]. Biochem Biophys Res Commun, 1996, 222(12): 249
[11] IiQF, Reis E, ZhngWX, et a.l Accelerated flap prefabrication with vascular endothelialgrowth factor[J]. JReconstrMicrosurg, 2000, 16(1): 451
[12] VonderZeeR, MuroharaT, Lou Z, eta.l VEGF/VPF augmentsno release from quiescent rabbit and human vascularendothelium[J].Circulation, 1997, 95(4):1030
[13] Neuffld G, Cohen T, Gengrinovitch S,et al. Vascular endothelial growth factor (VEGF) and its receptors[J]. FASEB J,1999, 13: 9-22
[14] Cross ML, Claesson-Welsh L. FGF and VEGF funcation in angiogenesis: signaling pathways, biological responses and therapeutic inhibition[J]. TRENDSPharma Sci, 2001, 22:201-207
[15] Schumacher B, Pecher P, von Specht BU,et al. Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heartdisease[J].Circulation, 1998, 97: 645-650
[16] Yoon YS,Johnson IA, Park JS,et al. Therapeutic myocardialangiogenesiswith vascular endothelial growth factors[ J]. MolCellBiochem, 2004, 264(1-2):63-74
[17] Helisch A, Schaper.W. Angiogenesis and arteriogenesis-not yet for prescrition.Z Kardiol 2000,89:239-244
[18] Peter JN, Michael CB, Jack G, et al. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science,1990, 247: 1219
[19] BaumannCI, BaileyAS, LiW,etal. PECAM-1 is expressed on hematopoieticstem cells throughoutontogeny and identifies a population oferythroid progenitors[J].Blood, 2004, 104(4): 1010-1016
[20] WattSM,CsehmeissnerSE,BatesPA.PECAM-l its exPression and function as a cell adhesion molecule on hemopoietic and endothelial ceells[J].LeukLymphoma,1995,17:229一244
[21] Rossler J, Lagodny J. Blood and lymph vessels in embryonic tumors. Hematol Oncol, 2005, 23 (3-4): 94-101
[22] Carmeliet P. Angiogenesis in life, disease and medicine.Nature, 2005, 438 (7070): 932-936
[23] Ferguson JE, Kelley RW, Patterson C. Mechanisms of endothelial differentiation in embryonic vasculogenesis Arterioscler Thromb Vasc Biol, 2005, 25 (11): 2246-2254
[24] Stoekinger H,GaddSJ,EherF. et al Molecular characterization and functional analysis,of the leukocyte cell,surface protein CD31J Immunol,1990,145-3889
[25] Albelda SM,Oliver PD,Romer LH,et al.EndoCAM:a novel endothelial cell-cell adhesion molecule.J Cell Biol,1990,110(4):1227-1237
[26] Delisser HM,Christofiduo-Solomidou M,Strieter RM,et al.Involvement of endothelial PECAM-1/CD31 in angiogenesis.Am J Pathol,1997,151(3):671-677
[27] Biswas P,Canosa S,Schoenfeld J,et al.PECAM-1 promotesβ-catenin accumulation and stimulates endothelial cell proliferation.Biochem Biophys Res Commun,2003,303(1):212–218
[28] Cao G,O’Brien CD,Zhou Z,et al.Involvement of human PECAM-1 inangiogenesis and in vitro endothelial cell migration.Am J Physiol Cell Physiol,2002,282(5):C1181-C1190
[29] Gratzinger D,Barreuther M,Madri JA,et al.Platelet endothelial cell adhesion molecule-1 modulates endothelial migration through its immunoreceptor tyrosine-based inhibitory motif.Biochem Biophys Res Commun,2003,301(1):243-249
[30] Ilan N,Mahooti S,Rimm D,et al.PECAM-1(CD31)functions as a reservoir forand a modulator of tyrosine-phosphorylated beta-catenin.J Cell Sci,1999,112(Pt 18):3005-3014
[31] Gratzinger D,Canosa S,Engelhardt B,et al.Platelet endothelial cell adhesion molecule-1 modulates endothelial cell motility through the small G-protein Rho.FASEB J,2003,17(11):1458-1469
[32] RayChaudhury A,Elkins M,Kozien D,et al.Regulation of PECAM-1 in endothelial cells during cell growth and migration[J].Exp Biol Med(Maywood),2001,226(7):686-691
[33] Cao G,O’Brien CD,Zhou Z,et al.Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration[J].Am J Physiol Cell Physiol,2002,282(5):C1181-C1190
[34] NwemnaPJ,Ne、v们nnaDK.SingaltransduetionPathwyasmediatedbyPECAM-l: NewrolesofrnaoldmoleeuleinPlateletnadvaseulareellbiolog.yAertrioselerThromb、Vasc Biol,2003,23:953一964
[35] Brown S,Heinisch I,RossE,et al.Apoptosis disables PECAM-1 mediated cell detachment from phagocytes promoting binding and engulfment. Nature, 2002, 418: 200-203
[36] Gao CJ,Sun WY,Christofidou-Solomidou M,et al.PECAM-1 functions as a specific and potent inhibitor of mitochondrial dependent apoptosis.Blood,2003,102:169-179
[1] LochMacdonald R. Management of cerebral vasospasm. Neurosur Rev, 2006, 29: 179-193
[2] Juul R, Edvinsson L, Jisrole SE. Calcitonin gene-related peptide-LI in SAH in man signs of activation of the trigeminal cerebrovascbular. Br J Nearosurg,1990,4(3):171
[3] Arienta C,Balli S,Caroli M,et al. Depletion of calcitoningene-related peptide in perivascular nerve during acute phase of posthemorrhagic vasospasm in the rabbit. Brain Res Bull,1991,27:605
[4] SatohM,Perkins E,Kimura H,et al.Posttreatment with adenovirus mediated gene transfer of calcitonin gene-related peptide reverse cerebral vasospasm in dogs[J].J Neurosurg,2002,97(1):136-142
[5] YotsumotoS, Shmi adaT, CuiCY, eta.l Expression ofadrenomedullin,a hypotensivepeptide, in the trophoblast giant cells at the embryo miplantation site inmouse. Dev Bio,l 1998, 203: 264-275
[6] NelsonMT, HuangY, Brayden JE, et a.l Arterial dilations in re-sponse to calcitonin gene-related peptide involve activation ofK+channels. Nature, 1990, 344: 770-773
[7] HongKW, YooSE, Yu SS, eta.l Pharmacologicalcouplingand functional role forCGRP receptors in the vasodilation of ratpial arterioles. Am J Physio,l 1996, 270: H317-H323
[8]吴军,周春奎,饶明俐,等.实验性SAH后CVS大鼠脑组织CGRPmRNA表达研究[J]中风与神经疾病杂志,1999,16(5):260-262
[9]李晓艳,黄从新,孙有刚,等.降钙素基因相关肽对人血管平滑肌细胞增殖的抑制作用[J].中国病理生理杂志, 2000, 16(1): 24-26
[10]邓水秀,秦旭平.降钙素基因相关肽的血管生物学功能多样性[J].国际病理科学与临床杂志,2006,26(3):246-249
[11]陈泽军,周岱.丝裂原活化蛋白激酶在脑血管病中的研究进展.博士学位论文,2006
[12]王德超,申文增,史树堂,等.大鼠弥漫性脑损伤后脑组织中MDA和SOD的变化.河北职工医学院学报,2005,22(4):1-2
[13]谭建新,李岩松,黄宇戈,等.降钙素基因相关肽对大鼠心肌缺血损伤的保护作用研究[J].中国当代儿科杂志,1999,1(1):27-29
[14] Gopalakrishnan V,Xu YJ,Sulakhe PV,et al. Vasopressin(V1) receptor characteristics in rat aortic smooth mucle cell[J].Am J Physiol,1991,261(Heart Circ,Physiol,30):H1927-H1936
[15]叶季鲜,李红梅,黄静,等.降钙素基因相关肽对血管升压素缩血管效应的影响[J].心脏杂志,2003,15(6):493-494
[16] Hendryk S,Jarzab B,Josko J.Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH.Neuro Endocrinol Lett.2004,25:141-147
[17] Fassbender K,Hodapp B,Rossol S,et al.Inflammatory cytokines in subarachnoid hemorrhage:association with abnormal blood flow velocities in basal cerebral arteries.J Neurol Neurosurg Psychiatry.2001,70:534–537
[18] Polin R,Bavbek M,Shaffrey M,et al.Detection of soluble E-selectin,ICAM-1,VCAM-1,and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage.J Neurosurg.1998,89:559–567
[19] Kaynar MY,Tanriverdi T,Kafadar AM,et al.Detection of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in both cerebrospinal fluidand serun of patients after aneurysmal subarachnoid hemorrhage . J Neurosurg.2004,101:1030-1036
[20]张晓钰,周东.降钙素基因相关肽对中枢神经系统的影响[J].国外医学神经病学神经外科学分册.2005,32(2):134-137
[21] ButtE, BernhardtM, SmolenskiA, et a.l Endothelial nitric-oxide synthase (typeⅢ) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases. J BiolChem, 2000, 275: 5179-5187
[22] Fujikawa H,Tam E,Yamaura I,et al. Activation of protein kinase in canine basilar artery in vasospasm.J cereb Blood Flow Metab,1999,19(1):44052
[23] Dietrich HH , Dacey CG . Molecular key to the problem of cerebral vasospasm. Neurosurgery, 2000,46(3):517-530
[24] Gilbert P, Tremblay J, Thorin E. Endothelium-detrived endothelin-1 reduces cerebral artery sensitivity to nitric oxide by a protein kinase C independent pathway. Stroke,2001,32(10):2351-2355
[25] RieehieriGL,etal. AerieanJournalofHernato10gy,1996;52(l):69
[26] Toshima M, Kassell NF, Tanaka Y, et al. Effect of intracisternal and intravenous calcitonin gene-related peptide on experimental cerebral vasospasm in rabbits. Act Neurochir (Wien),1992,119(1-4):134
[27] Imaizumi S,Shimizu H,Ahmad I,et al. Effect of calcitonin gene-related peptide on delayed cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. Surg Neurol,1996,46(3):263
[28] Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev, 2004,84(3):903-934
[29] Tang Y, Han C, Wang X. role of nitric oxide and prostaglandins in the potentiating effects of Calcitonin gene-related peptide on lipopolysaceharide-induced interleukin-6 release from mouse peritoneal macrophages. Immuoligy, 1999,96∶1 71~175
[30] Pfister HW,Kiimpfel T,Koedel U. Neuroreport,1995,6:1302-1305.
[31] Edvinsson L,Delgado-Zygmunt T,Ekman R,et al. Involvement of perivascular sensory fibers in the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage. J Cereb Blood Flow Metab,1990,10:602
[32]邓水秀,秦旭平,等.降钙素基因相关肽的血管生物学功能多样性[J]国际病理科学与临床杂志,2006,26(3):246-249
[33]林平,赵守琪,刘洋,等.CGRP对葡萄糖诱导血管内皮细胞凋亡保护作用的研究[J].哈尔滨医科大学学报, 2005, 39(2): 118-120, 123
[2] Hansen-Schwartz J. Cerebral vasospasm: a consideration of the various cellular mechanisms involved in the pathophysiology.Neurocrit Care, 2004,1:235-246
[3] Crowley RW, Medel R, Kassell NF, el al. New insights intothe causes and therapy of cerebral vasospasm following sub-arachnoid hemorrhage. Drug Discov Today, 2008, 13 ( 5-6 ): 254-260
[4] Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev, 2004,84(3):903-934
[5] Yu XJ, Li CY, Wang KY, Dai HY. Calcitonin gene-related peptide regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes by activation of ERK1/2 MAPK. Regul Pept,2006,137(3):134-139
[6]邓水秀,秦旭平.降钙素基因相关肽的血管生物学功能多样性.国际病理科学与临床杂志,2006, 26(3):246-249
[7] Juul R, Edvinsson L, Jisrole S. Calcitonin gene-relat-ed peptide-LI in SAH in man signs of activation of thetrigemino cerebrovascular[J].Br J Neurosurg, 1990,4(3): 171-179
[8] Arienta C, Balbi S, Caroli M,et al. Depletion of cal-citonin gene-related peptide in perivascular never dur-ing acute phase of post-hemorrhagic vasospasm in therabbit[J].Brain Res Bull, 1991,27(5): 605-609
[9] Mathison S, Nagilla R, Kompella UB. Nasal route for direct delivery of solutes to the central nervous system: fact or fiction? J Drug Target,1998,5(6):415-441
[10]贾莉,孙保亮.中枢神经系统淋巴引流的研究进展.中国微循环, 2006,10(5): 377-380
[11] Nakayama T, Illoh K, Ruetzler C, Auh S, Sokoloff L, Hallenbeck J. Intranasal administration of E-selectin to induce immunological tolerization can suppress subarachnoid hemorrhage-induced vasospasm implicating immune and inflammatory mechanisms in its genesis. Brain Res, 2007, 1132(1):177-184
[12] Banks WA. The CNS as a target for peptides and peptide-based drugs. Expert Opin Drug Deliv,2006,3(6):707-712
[13]王峰,蒋新国.鼻勃膜作为脑内递药途径的研究进展. [J]药学学报,2001,36(8):636-640
[14] Vatter H, Weidauer S, Konczalla J, et al. Time course in the development of cerebral vasospasm after experimental subarachnoid hemorrhage: clinical and neuroradiologica assessment of therat double hemorrhage model [ J ]. Neurosurgery,2006,58(6):1190-1197
[15] Lu LF, Fiscus RR. Nitric oxide donors enhance calcitonin gene-re-lated peptide-induced elevations of cyclic AMP invascular smoothmuscle cells [J]. Eur J Pharmacol,1999,376(3):307-314
[16] Rosenblum WI, Shimizu T, Nelson GH. Endothelium-depend-ent effects of substance P and calcitonin gene-related peptide omouse pial arterioles [J]. Stroke,1993,24(7):1043-1047
[17] Holland JP, Sydserff SG, Taylor WS,et al. Calcitonin gene-re-lated peptide reduces brain injury in a rat model of focal cere-bral ischemia [J]. Stroke,1994,25(10):2055-2059
[18]武晓玉,高永良经鼻私膜递送人脑给药途径的研究进展「J」中国药学杂志,2003,38(8):561一564
[19] IllumL Transporoofdrogsfron henasalcavitytoth entra-nervousSystem「JEu:JPhar,Sci,2000,11(1):1一18
[20] Roux S,et al.The role of endothelin cerebral vasospasm[J].Neurosurgery.1995:37-78
[21]安蔚,孙保亮,杨明峰..经斜坡法大鼠基底动脉在体观测方法的建立[J]泰山医学院学报,2005,26:278-280
[22] Sun BL, Zhang SM, Xia ZL, et a.l The effects ofnimodip-ine on regional cerebralblood flow, brainwater and electro-lytes contents in rats with subarachnoid hemorrhage[ J].ClinHemorheoMicrocirc, 2003, 29(3,4): 337-344
[23] MEGURO T,CLOWER B R,CARPENTER R,et al.Im-proved rat model for cerebralvasospasm studies[J].Neurol Res,2001,23(7):761-766
[24] PRUNELL G F,MATHIESEN T,SVENDGAARD N A.Anew experimental model in rats for study of the pathophy-siology of subarachnoid hemorrhage[J].Neuroreport,2002,13(18):2553-2556
[25] PRUNELL G F ,MATHIESEN T ,DIEMER N H ,et al .Experimental subarachnoidhemorrhage:subarachnoid blood volume,mortality rate,neuronal death,cerebral blood flow , and perfusion pressure in three different rat models[J]. Neurosurgery,2003,52(1):165-176
[26] Gules I,Satoh M,Clower BR,et al.Comparison of three ratmodels of cerebral vasospasm[J].Am J Physiol Heart CircPhysiol,2002;283(6):2551-2559
[27] Meguro T,Clower BR,Carpenter R,et al.Improved rat model for cerebral vasospasm studies[J].Neurol Res,2001;23(7):761-766
[28] Suzuki H,Kanamaru K,Tsunoda H,et al.Heme oxyge-nase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats[J].J Clin Invest,1999;104(1):59-66
[29]Harada S,Kamiya K,Masago A,et al.Subarachnoid hemor-rhage induces c-fos,c-jun and hsp70 mRNA expression in rat brain[J].Neuroreport,1997;8(15):3399-3404
[30]武晓玉,高永良经鼻私膜递送人脑给药途径的研究进展「J」中国药学杂志,2003,38(8):561一564
[31]朱长庚,神经解剖学[M]北京:人民卫生出版社,2002.838-839
[32]相小强,陶涛,陈庆华.透血脑屏障制剂的研究进展[J].中国新药杂志,2002,11(7):519
[33] ILLUM L·Nasal drug delivery-possibilities, problems and solutions[J]·J Controlled Release, 2003, 87(1-3): 187-198
[34] Juul R, Edvinsson L, Jisrole SE. Calcitonin gene-related peptide-LI in SAH in man signs of activation of the trigeminal cerebrovascbular. Br J Nearosurg,1990,4(3):171
[35] Arienta C,Balli S,Caroli M,et al. Depletion of calcitonin gene-related peptide in perivascular nerve during acute phase of posthemorrhagic vasospasm in the rabbit. Brain Res Bull,1991,27:605
[36] Edvinsson L, Ekman R, Jansen I, et a.l Reduced levels of calci-tonin gene - related peptide - like immunoreactivity in human brain vessels after subarachnoid haemorrhage[J]. Neurosci Lett,1991, 121: 151-154
[37] Pluta RM, Dejam A, GrimesG, eta.l Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage[J]. JAMA, 2005,293(12): 1477-1484
[38] DeHoon JN,Pickkers P,Smits P,et al.Calcitonin gene-related pep-tide:Exploring its vasodilatingmechanism of action in humans[J].Clin Pharmacol Ther,2003,73(4):312-321
[39] SatohM,Perkins E,Kimura H,et al.Posttreatment with adenovirus-mediated gene transfer of calcitonin gene-related peptide reverse cere-bral vasospasm in dogs[J].J Neurosurg,2002,97(1):136-142
[40]王轩,张颜波,孙保亮,等.蛛网膜下腔出血后脑血管痉挛分子机制的研究进展[J].中国微循环,2007,11(3):216-218
[41]邓水秀,秦旭平.降钙素基因相关肽的血管生物学功能多样性[J].国际病理科学与临床杂志,2006,26(3):246-249.
[42]王德超,申文增,史树堂,等.大鼠弥漫性脑损伤后脑组织中MDA和SOD的变化[J].河北职工医学院学报,2005,22(4):1-2
[43]叶季鲜,李红梅,黄静,等.降钙素基因相关肽对血管升压素缩血管效应的影响[J].心脏杂志,2003,15(6):493-494
[44] Hendryk S,Jarzab B,Josko J.Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH[J].Neuro Endocrinol Lett.2004,25:141-147
[45] Fassbender K,Hodapp B,Rossol S,et al.Inflammatory cytokines in subarachnoid hemorrhage:association with abnormal blood flow velocities in basal cerebral arteries[J].J Neurol Neurosurg Psychiatry.2001,70:534–537
[46] Kaynar MY,Tanriverdi T,Kafadar AM,et al.Detection of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in both cerebrospinal fluidand serun of patients after aneurysmal subarachnoid hemorrhage[J].J Neurosurg.2004,101:1030-1036
[47]张晓钰,周东.降钙素基因相关肽对中枢神经系统的影响[J].国外医学神经病学神经外科学分册.2005,32(2):134-137
[48] ButtE,BernhardtM,SmolenskiA,et al.Endothelial nitric-oxide synthase (typeⅢ) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases[J].J BiolChem,,2000,,275:5179-5187
[49]Dietrich HH , Dacey CG . Molecular key to the problem of cerebralvasospasm.Neurosurgery[J]. 2000,46(3):517-530
[50] Gilbert P,Tremblay J,Thorin E.Endothelium-detrived endothelin-1 reduces cerebral artery sensitivity to nitric oxide by a protein kinase C independent pathway[J].Stroke.2001,32(10):2351-2355
[51] Brain SD,Grant AD.Vascular actions of calcitonin gene-related peptide and adrenomedullin[J].Physiol Rev,2004,84(3):903-934
[52]林平,赵守琪,刘洋,等.CGRP对葡萄糖诱导血管内皮细胞凋亡保护作用的研究[J].哈尔滨医科大学学报,2005,39(2):118-120
[53] Schoch B, Regel JP, W ichertM,el al.Analysis of intrathe-cal interleukin-6 as a potential predictive factor for vasospasm in subarachnoid hemorrhage. Neurosurgery, 2007, 60 ( 5 ):828-836
[54] ChristopherG,HarrodMS, Bemard R, et al. Prediction of cerebral vasospasm in patients presenting with aneurymal subarachnoid hemorrhage: a review. Neurosurg, 2005, 56 ( 4 ): 633-652
[55] GreenbergMS·Handbook ofNeurosurg[M]·NewYork: ThiemeMedicalpublish, 2000
[56] Zhang JH·Progress in reuroscience [M ]. BeiJing: Higher EducationPress, 2004
[57] Hoh BL,TopcuogluMA, SinghalAB, etal·Effectofclipping,Craniotomy,or intravascular coiling on cerebral vasospasm and patient outcome after aneurismal subarachnoid hemorrhage[ J]·Neurosurg, 2004, 55(4): 779-786
[59] Dorsch AD, NicholasWC·Therpeutic approaches to vasospasm in subarachnoid hemorrhage·Current Opinion in Critical[ J]·Care, 2002, 8(2): 128-133
[1] Maruotti N, Cantatore FP, Crivellato E,et al. Angiogenesis inrheumatoid arthritis[J]. HistolHistopatho,l 2006, 21(5): 557-566
[2]刘文韬,陈国玉,夏建国,等.胃癌微卫星不稳定性与血管内皮生长因子表达关系的研究[J].医学研究生学报, 2007, 18(2): 37-40
[3]高媛,高建忠,孙启鸿.血小板内皮细胞黏附分子1(PECAM-1)的研究[J].细胞与分子免疫学杂志, 2005, 21(3): 40-42
[4] Thompson RD, WakelinMW, LarbiKY,et al. Divergent effects of platelet-endothelial cell adhesion molecule-1 and 3 integrin blockade on leukocyte transmigrationin vivo[J].J Immunol, 2000, 165(1):426-434
[5] CaoG, O’Brien CD, Zhou Z,etal. Involvementofhuman PECAM-1 in angiogenesis andin vitroendothelial cellmigration[J].PhysiolCellPhysiol, 2002, 282(5):C1181-C1190
[6] Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases[J].Nature, 2000, 407(6801): 249-257
[7] NeufeldqCohenT,GengrinovitehS,etal.Vascularendothelial growthfactor(VEGF)anditsrecePtors.FasebJJan1999;13(1):9一22
[8] Rossler J, Lagodny J. Blood and lymph vessels in embryonic tumors. Hematol Oncol, 2005, 23 (3-4): 94-101
[9] Carmeliet P. Angiogenesis in life, disease and medicine.Nature, 2005, 438 (7070): 932-936
[10] SiemeisterG, SehnurrB, MohrsK, eta.l Expression ofbiologically active isoforms of the tumor angiogenesis factor VEGF in Escherichia coli[J]. Biochem Biophys Res Commun, 1996, 222(12): 249
[11] IiQF, Reis E, ZhngWX, et a.l Accelerated flap prefabrication with vascular endothelialgrowth factor[J]. JReconstrMicrosurg, 2000, 16(1): 451
[12] VonderZeeR, MuroharaT, Lou Z, eta.l VEGF/VPF augmentsno release from quiescent rabbit and human vascularendothelium[J].Circulation, 1997, 95(4):1030
[13] Neuffld G, Cohen T, Gengrinovitch S,et al. Vascular endothelial growth factor (VEGF) and its receptors[J]. FASEB J,1999, 13: 9-22
[14] Cross ML, Claesson-Welsh L. FGF and VEGF funcation in angiogenesis: signaling pathways, biological responses and therapeutic inhibition[J]. TRENDSPharma Sci, 2001, 22:201-207
[15] Schumacher B, Pecher P, von Specht BU,et al. Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heartdisease[J].Circulation, 1998, 97: 645-650
[16] Yoon YS,Johnson IA, Park JS,et al. Therapeutic myocardialangiogenesiswith vascular endothelial growth factors[ J]. MolCellBiochem, 2004, 264(1-2):63-74
[17] Helisch A, Schaper.W. Angiogenesis and arteriogenesis-not yet for prescrition.Z Kardiol 2000,89:239-244
[18] Peter JN, Michael CB, Jack G, et al. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science,1990, 247: 1219
[19] BaumannCI, BaileyAS, LiW,etal. PECAM-1 is expressed on hematopoieticstem cells throughoutontogeny and identifies a population oferythroid progenitors[J].Blood, 2004, 104(4): 1010-1016
[20] WattSM,CsehmeissnerSE,BatesPA.PECAM-l its exPression and function as a cell adhesion molecule on hemopoietic and endothelial ceells[J].LeukLymphoma,1995,17:229一244
[21] Rossler J, Lagodny J. Blood and lymph vessels in embryonic tumors. Hematol Oncol, 2005, 23 (3-4): 94-101
[22] Carmeliet P. Angiogenesis in life, disease and medicine.Nature, 2005, 438 (7070): 932-936
[23] Ferguson JE, Kelley RW, Patterson C. Mechanisms of endothelial differentiation in embryonic vasculogenesis Arterioscler Thromb Vasc Biol, 2005, 25 (11): 2246-2254
[24] Stoekinger H,GaddSJ,EherF. et al Molecular characterization and functional analysis,of the leukocyte cell,surface protein CD31J Immunol,1990,145-3889
[25] Albelda SM,Oliver PD,Romer LH,et al.EndoCAM:a novel endothelial cell-cell adhesion molecule.J Cell Biol,1990,110(4):1227-1237
[26] Delisser HM,Christofiduo-Solomidou M,Strieter RM,et al.Involvement of endothelial PECAM-1/CD31 in angiogenesis.Am J Pathol,1997,151(3):671-677
[27] Biswas P,Canosa S,Schoenfeld J,et al.PECAM-1 promotesβ-catenin accumulation and stimulates endothelial cell proliferation.Biochem Biophys Res Commun,2003,303(1):212–218
[28] Cao G,O’Brien CD,Zhou Z,et al.Involvement of human PECAM-1 inangiogenesis and in vitro endothelial cell migration.Am J Physiol Cell Physiol,2002,282(5):C1181-C1190
[29] Gratzinger D,Barreuther M,Madri JA,et al.Platelet endothelial cell adhesion molecule-1 modulates endothelial migration through its immunoreceptor tyrosine-based inhibitory motif.Biochem Biophys Res Commun,2003,301(1):243-249
[30] Ilan N,Mahooti S,Rimm D,et al.PECAM-1(CD31)functions as a reservoir forand a modulator of tyrosine-phosphorylated beta-catenin.J Cell Sci,1999,112(Pt 18):3005-3014
[31] Gratzinger D,Canosa S,Engelhardt B,et al.Platelet endothelial cell adhesion molecule-1 modulates endothelial cell motility through the small G-protein Rho.FASEB J,2003,17(11):1458-1469
[32] RayChaudhury A,Elkins M,Kozien D,et al.Regulation of PECAM-1 in endothelial cells during cell growth and migration[J].Exp Biol Med(Maywood),2001,226(7):686-691
[33] Cao G,O’Brien CD,Zhou Z,et al.Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration[J].Am J Physiol Cell Physiol,2002,282(5):C1181-C1190
[34] NwemnaPJ,Ne、v们nnaDK.SingaltransduetionPathwyasmediatedbyPECAM-l: NewrolesofrnaoldmoleeuleinPlateletnadvaseulareellbiolog.yAertrioselerThromb、Vasc Biol,2003,23:953一964
[35] Brown S,Heinisch I,RossE,et al.Apoptosis disables PECAM-1 mediated cell detachment from phagocytes promoting binding and engulfment. Nature, 2002, 418: 200-203
[36] Gao CJ,Sun WY,Christofidou-Solomidou M,et al.PECAM-1 functions as a specific and potent inhibitor of mitochondrial dependent apoptosis.Blood,2003,102:169-179
[1] LochMacdonald R. Management of cerebral vasospasm. Neurosur Rev, 2006, 29: 179-193
[2] Juul R, Edvinsson L, Jisrole SE. Calcitonin gene-related peptide-LI in SAH in man signs of activation of the trigeminal cerebrovascbular. Br J Nearosurg,1990,4(3):171
[3] Arienta C,Balli S,Caroli M,et al. Depletion of calcitoningene-related peptide in perivascular nerve during acute phase of posthemorrhagic vasospasm in the rabbit. Brain Res Bull,1991,27:605
[4] SatohM,Perkins E,Kimura H,et al.Posttreatment with adenovirus mediated gene transfer of calcitonin gene-related peptide reverse cerebral vasospasm in dogs[J].J Neurosurg,2002,97(1):136-142
[5] YotsumotoS, Shmi adaT, CuiCY, eta.l Expression ofadrenomedullin,a hypotensivepeptide, in the trophoblast giant cells at the embryo miplantation site inmouse. Dev Bio,l 1998, 203: 264-275
[6] NelsonMT, HuangY, Brayden JE, et a.l Arterial dilations in re-sponse to calcitonin gene-related peptide involve activation ofK+channels. Nature, 1990, 344: 770-773
[7] HongKW, YooSE, Yu SS, eta.l Pharmacologicalcouplingand functional role forCGRP receptors in the vasodilation of ratpial arterioles. Am J Physio,l 1996, 270: H317-H323
[8]吴军,周春奎,饶明俐,等.实验性SAH后CVS大鼠脑组织CGRPmRNA表达研究[J]中风与神经疾病杂志,1999,16(5):260-262
[9]李晓艳,黄从新,孙有刚,等.降钙素基因相关肽对人血管平滑肌细胞增殖的抑制作用[J].中国病理生理杂志, 2000, 16(1): 24-26
[10]邓水秀,秦旭平.降钙素基因相关肽的血管生物学功能多样性[J].国际病理科学与临床杂志,2006,26(3):246-249
[11]陈泽军,周岱.丝裂原活化蛋白激酶在脑血管病中的研究进展.博士学位论文,2006
[12]王德超,申文增,史树堂,等.大鼠弥漫性脑损伤后脑组织中MDA和SOD的变化.河北职工医学院学报,2005,22(4):1-2
[13]谭建新,李岩松,黄宇戈,等.降钙素基因相关肽对大鼠心肌缺血损伤的保护作用研究[J].中国当代儿科杂志,1999,1(1):27-29
[14] Gopalakrishnan V,Xu YJ,Sulakhe PV,et al. Vasopressin(V1) receptor characteristics in rat aortic smooth mucle cell[J].Am J Physiol,1991,261(Heart Circ,Physiol,30):H1927-H1936
[15]叶季鲜,李红梅,黄静,等.降钙素基因相关肽对血管升压素缩血管效应的影响[J].心脏杂志,2003,15(6):493-494
[16] Hendryk S,Jarzab B,Josko J.Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH.Neuro Endocrinol Lett.2004,25:141-147
[17] Fassbender K,Hodapp B,Rossol S,et al.Inflammatory cytokines in subarachnoid hemorrhage:association with abnormal blood flow velocities in basal cerebral arteries.J Neurol Neurosurg Psychiatry.2001,70:534–537
[18] Polin R,Bavbek M,Shaffrey M,et al.Detection of soluble E-selectin,ICAM-1,VCAM-1,and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage.J Neurosurg.1998,89:559–567
[19] Kaynar MY,Tanriverdi T,Kafadar AM,et al.Detection of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in both cerebrospinal fluidand serun of patients after aneurysmal subarachnoid hemorrhage . J Neurosurg.2004,101:1030-1036
[20]张晓钰,周东.降钙素基因相关肽对中枢神经系统的影响[J].国外医学神经病学神经外科学分册.2005,32(2):134-137
[21] ButtE, BernhardtM, SmolenskiA, et a.l Endothelial nitric-oxide synthase (typeⅢ) is activated and becomes calcium independent upon phosphorylation by cyclic nucleotide-dependent protein kinases. J BiolChem, 2000, 275: 5179-5187
[22] Fujikawa H,Tam E,Yamaura I,et al. Activation of protein kinase in canine basilar artery in vasospasm.J cereb Blood Flow Metab,1999,19(1):44052
[23] Dietrich HH , Dacey CG . Molecular key to the problem of cerebral vasospasm. Neurosurgery, 2000,46(3):517-530
[24] Gilbert P, Tremblay J, Thorin E. Endothelium-detrived endothelin-1 reduces cerebral artery sensitivity to nitric oxide by a protein kinase C independent pathway. Stroke,2001,32(10):2351-2355
[25] RieehieriGL,etal. AerieanJournalofHernato10gy,1996;52(l):69
[26] Toshima M, Kassell NF, Tanaka Y, et al. Effect of intracisternal and intravenous calcitonin gene-related peptide on experimental cerebral vasospasm in rabbits. Act Neurochir (Wien),1992,119(1-4):134
[27] Imaizumi S,Shimizu H,Ahmad I,et al. Effect of calcitonin gene-related peptide on delayed cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. Surg Neurol,1996,46(3):263
[28] Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev, 2004,84(3):903-934
[29] Tang Y, Han C, Wang X. role of nitric oxide and prostaglandins in the potentiating effects of Calcitonin gene-related peptide on lipopolysaceharide-induced interleukin-6 release from mouse peritoneal macrophages. Immuoligy, 1999,96∶1 71~175
[30] Pfister HW,Kiimpfel T,Koedel U. Neuroreport,1995,6:1302-1305.
[31] Edvinsson L,Delgado-Zygmunt T,Ekman R,et al. Involvement of perivascular sensory fibers in the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage. J Cereb Blood Flow Metab,1990,10:602
[32]邓水秀,秦旭平,等.降钙素基因相关肽的血管生物学功能多样性[J]国际病理科学与临床杂志,2006,26(3):246-249
[33]林平,赵守琪,刘洋,等.CGRP对葡萄糖诱导血管内皮细胞凋亡保护作用的研究[J].哈尔滨医科大学学报, 2005, 39(2): 118-120, 123