破裂颅内动脉瘤瘤壁核因子κB与血管内皮生长因子的表达

目的 探讨核因子kB(NF-kB)和血管内皮生长因子(VEGF)在破裂颅内动脉瘤瘤壁的表达及相关性,并观察两者与瘤壁血管重塑的关系.方法 采用免疫组织化学方法对26例DSA和手术证实的颅内动脉瘤瘤壁标本的NF-kB和VEGF表达进行检测,10例因脑外伤手术切除颞极的颞叶皮层动脉血管标本作对照,光镜下观察各组染色结果并作统计学分析,同时行常规组织学检查观察瘤壁粥样硬化病变特点.结果 动脉瘤组标本NF-k＞B和VEGF阳性表达分别为23/26和21/26,10例正常对照组标本中NF-k＞B和VEGF仅有微弱表达,差异有统计学意义(P＜0.01); NF-kB和VEGF在颅内动脉瘤瘤壁中的表达均以内膜、中膜较高,外膜表达较少,两者在瘤壁中的表达有正相关性,相关系数为0.740.组织学检查发现瘤壁出现程度不同的动脉粥样硬化改变.结论 动脉粥样硬化是颅内动脉瘤伴随的重要病理改变.NF-kB和VEGF在颅内动脉瘤发病和粥样硬化病变过程中可能发挥了重要的协同作用.     

破裂颅内动脉瘤瘤壁核因子kB与血管内皮生长因子的表达

目的 探讨核因子kB(NF-kB)和血管内皮生长因子(VEGF)在破裂颅内动脉瘤瘤壁的表达及相关性,并观察两者与瘤壁血管重塑的关系.方法 采用免疫组织化学方法对26例DSA和手术证实的颅内动脉瘤瘤壁标本的NF-kB和VEGF表达进行检测,10例因脑外伤手术切除颞极的颞叶皮层动脉血管标本作对照,光镜下观察各组染色结果并作统计学分析,同时行常规组织学检查观察瘤壁粥样硬化病变特点.结果 动脉瘤组标本NF-k＞B和VEGF阳性表达分别为23/26和21/26,10例正常对照组标本中NF-k＞B和VEGF仅有微弱表达,差异有统计学意义(P＜0.01); NF-kB和VEGF在颅内动脉瘤瘤壁中的表达均以内膜、中膜较高,外膜表达较少,两者在瘤壁中的表达有正相关性,相关系数为0.740.组织学检查发现瘤壁出现程度不同的动脉粥样硬化改变.结论 动脉粥样硬化是颅内动脉瘤伴随的重要病理改变.NF-kB和VEGF在颅内动脉瘤发病和粥样硬化病变过程中可能发挥了重要的协同作用.     

基质金属蛋白酶-9和血管内皮生长因子在颅内动脉瘤中的表达

目的通过观察基质金属蛋白酶-9(MMP-9)和血管内皮生长因子(VEGF)在颅内动脉瘤中的表达情况,并且与正常脑动脉血管组织中两者的表达相比较,为研究动脉瘤的发病原因及机制提供线索。方法用免疫组织化学方法对16例经手术和病理证实的脑动脉瘤标本中的MMP-9、VEGF的表达进行检测,同时将7例颞叶癫痫间患者手术切除颞极的颞叶皮层动脉血管组织标本作为相对正常脑动脉血管组织的对照,进行MMP-9、VEGF的表达检测,将所得染色标本在光镜下观察,并用医学图像分析系统进行定量分析。结果7例正常脑动脉血管组织中无MMP-9、VEGF阳性表达,而动脉瘤的MMP-9、VEGF阳性表达率分别为81.2%(13/16)和87.5%(14/16),2组标本相对照具有显著差异(P<0.05);MMP9-在动脉瘤壁内、中、外膜中均有表达,其中外、中膜阳性表达较高;VEGF主要在动脉瘤壁中、外膜表达,而内膜表达较少。结论动脉瘤的发生、生长和破裂是个很复杂的过程,MMP-9及VEGF可能是主要的影响因素之一,两者可能与动脉瘤的发生,增长以及结构维持有关。     

VEGF、MMP-9在人脑胶质瘤中的表达及其意义

目的探讨血管内皮细胞生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)在人脑胶质瘤中的表达及其与血管生成、瘤周水肿(PTBE)和肿瘤恶性程度的关系。方法采用免疫组化方法分别检测30例经手术和病理证实的脑胶质瘤瘤体和瘤周水肿区中VEGF、MMP-9的表达;通过计数微血管密度(MVD)来评估血管生成情况;根据CT和MRI的结果测定水肿指数;同时用透射电镜对瘤体区及瘤周水肿区的超微结构进行观察。6例来自颅脑损伤病人的正常脑组织作为对照。结果随着肿瘤级别增加MVD逐渐升高,在高级别胶质瘤体中MVD显著高于瘤周(P0.01);VEGF、MMP-9表达与胶质瘤中的MVD均呈显著正相关(P0.01),且两者与胶质瘤的水肿指数(EI)也均呈显著正相关(P0.01);高级别胶质瘤的EI显著高于低级别胶质瘤(Ⅰ级、Ⅱ级)(P0.05)。电镜下水肿明显者微血管内皮细胞胞浆内有较多小泡囊状细胞器和基底膜中有较多虫蚀样空洞等。结论 VEGF、MMP-9可能共同参与了脑胶质瘤血管生成和脑水肿的发生,并促进肿瘤的侵袭性生长。     

血管生长因子和结构蛋白在新疆哈萨克族破裂和未破裂颅内动脉瘤中的表达

目的 评价血管生长因子(VEGF,TGF -a)和结构蛋白(Ⅲ、Ⅳ型胶原,平滑肌肌动蛋白-a)在哈萨克族未破裂和破裂脑动脉瘤中的表达差异性,探讨脑动脉瘤生长和破裂的可能机制.方法 对12例哈萨克族多发脑动脉瘤患者术中同时获得的12对破裂与未破裂动脉瘤标本和尸体中所获得的5例正常脑动脉标本进行血管因子(VEGF和TGF-a)和结构蛋白(Ⅲ、Ⅳ型胶原,平滑肌肌动蛋白-a)进行免疫组化学染色.结果 VEGF在正常血管壁中无表达,在未破裂动脉瘤中表达较弱,而在破裂动脉瘤中表达较明显.TGF-a在正常血管壁中表达明显,在未破裂动脉瘤中表达较明显,而在破裂动脉瘤中表达较弱.Ⅲ、Ⅳ型胶原在正常血管壁中表达明显,而在未破裂动脉瘤中表达较明显,在破裂动脉瘤中表达较弱.SMC -a在正常动脉壁中表达明显,在未破裂动脉瘤中表达较明显,而在破裂动脉瘤中表达较弱.结论 血管生长因子的异常表达和血管壁基质结构蛋白的降解是脑动脉瘤形成与破裂的主要机制之一.     

体外培养人脑动静脉畸形血管内皮细胞中VEGF表达增加

目的探讨体外培养的人脑动静脉畸形血管内皮细胞和正常脑血管内皮细胞中血管内皮细胞生长因子(VEGF)表达水平的差异。方法采用组织块贴壁法对人脑动静脉畸形血管内皮细胞进行培养和形态学观察;免疫组化检测CD31和vWF抗原验证内皮细胞;采用RT-PCR和Western blot技术检测脑动静脉畸形血管内皮细胞VEGF mRNA和蛋白表达,并与和正常脑血管内皮细胞进行比较。结果体外培养的内皮细胞CD31和vWF染色阳性率达95%以上。人脑动静脉畸形血管内皮细胞中VEGF mRNA和蛋白表达均显著升高(P0.05)。结论体外培养的人脑动静脉畸形内皮细胞中VEGF的高表达,提示血管生成在脑动静脉畸形的发病机制中起重要作用。     

颅内动脉瘤组织超微结构及MMP-9表达相关调控机制的研究

目的 探讨颅内动脉瘤组织超微结构及MMP-9过度表达的相关调控机制.方法 观察颅内动脉瘤标本和正常脑血管的血管壁细胞外基质的形态学变化,检测脑血管壁组织内的CD68、MMP-gmRNA表达水平及c-Jun免疫活性,进行相关统计学分析.结果 电镜下见颅内动脉瘤血管壁的内皮细胞、平滑肌细胞凋亡和细胞外基质(ECM)破坏,CD68在颅内动脉瘤组织内14.60±1.72/高倍视野,正常脑血管壁内未见CD68阳性表达(P<0.01);c-Jun免疫活性在颅内动脉瘤组织内为1.92±051,正常脑血管壁内为0.17±0.41(P<0.01);动脉瘤组织中MMP-9mRNA的表达是正常对照的10.06倍(P<0.01);CD68和MMP-9mRNA之间呈显著正相关(r<,1>=0.931);颅内动脉瘤组织内c-Jun和MMP-9mRNA之间呈显著正相关(r<,2>=0.818).结论 颅内动脉瘤瘤壁组织中阳性表达的CD68可能通过激活c-Jun进而诱导MMP-9的大量表达破坏ECM参与颅内动脉瘤的发病机制.     

胶质瘤VEGF基因表达与血管生成和脑水肿的关系

目的　探讨胶质瘤血管内皮细胞生长因子(VEGF)基因表达与血管生成和脑水肿的关系。方法　采用Northernblot和ABC免疫组化方法检测34例人脑胶质瘤和8例正常脑组织中VEGF基因表达;Ⅷ因子相关抗原单克隆抗体组织化学染色显示微血管,用微血管计数(MVC)测定肿瘤血管生成;从脑水肿与肿瘤本身的体积之比获得水肿指数(EI),估价脑水肿的程度。结果　34例脑胶质瘤和8例正常脑组织均可表达3.9Kb的VEGFmRNA片段。VEGFmRNA表达与脑胶质瘤的血管生成、瘤周脑水肿均呈显著正相关(r=0.836,P＜0.01;r=0.890,P＜0.01);高恶度胶质瘤VEGFmRNA表达、MVC、EI分别显著高于低恶度胶质瘤(P＜0.01);低恶度胶质瘤VEGFmRNA表达、MVC均显著高于正常脑组织(P＜0.05)。免疫组化染色显示,VEGF蛋白主要分布在高恶度胶质瘤组织的瘤细胞和内皮细胞,低恶度胶质瘤呈低水平表达。结论　VEGF可能通过参与胶质瘤血管生成和脑水肿发生,对胶质瘤的恶性演进起促进作用。     

血管内皮细胞生长因子对胶质瘤病理形态影响的实验研究

目的了解血管内皮细胞生长因子(VEGF)对胶质瘤病理形态的影响。方法利用光镜和电镜观察转染有反义VEGF cDNA片段的C_6胶质瘤细胞的裸鼠移植瘤的病理特征,ELISA法检测肿瘤组织中VEGF的含量。结果转染有反义VEGF cDNA片段的C_6胶质瘤组织中VEGF含量明显低于仅转染有空载体的C_6胶质瘤组织(P＜0．05)。前者瘤组织表面存在类包膜,瘤周血管反应轻。无明显瘤周水肿,瘤周侵袭少见,凋亡瘤细胞明显增多；血管内皮细胞胞浆内VVO样结构少见,基板不连续、单层,外周见胶原纤维；但个别肿瘤大者瘤组织中VEGF含量也高,且内皮细胞VVO样结构也随之增多。而后者瘤周血管反应明显,瘤体和瘤周水肿严重,瘤细胞可侵袭瘤周组织,瘤内组织明显出血坏死,且可见瘤细胞形成类微血管样结构,血管内皮细胞胞浆内VVO样结构较多,水肿越明显VVO样结构越多见,并与组织中VEGF含量相一致；基板较完整连续,多数基质疏松,呈多层排列,外层见少量胶原纤维。所观察的几种肿瘤中的微血管内皮细胞孔窗及内皮细胞裂隙与转染的目的基因无明显的关系,且内皮细胞的凋亡均不明显。结论胶质瘤细胞上VEGF表达的下调可促进胶质瘤细胞凋亡；VEGF通过内皮细胞内的VVO样结构增多引起血管渗透性增加致瘤体和瘤周水肿,而与内皮细胞上孔窗无明显的关系：胶质瘤组织中的血管基板完整连续与否与VEGF有关。     

缺氧诱导人脑动静脉畸形血管内皮细胞生长因子表达

目的 探讨缺氧条件下体外培养的人脑动静脉畸形（cAVM）血管内皮细胞中血管内皮细胞生长因子（VEGF）基因表达与细胞超微结构变化。方法 采用组织块贴壁法对cAVM血管内皮细胞进行培养和形态学观察。采用免疫组化方法检测细胞中第八因子相关抗原（FⅧ-RA）的表达，采用RT-PCR技术观察静态和缺氧状态下2h、4h、8h血管内皮细胞VEGF mRNA表达。采用酶联免疫吸附实验（ELISA）检测每组细胞上清液中VEGF蛋白含量；在透射电镜下观察细胞超微结构的变化。结果 体外培养的活细胞具有单层“卵石样”排列的典型特征．95％以上的细胞FⅧ-RA染色阳性。血管内皮细胞vEGF蛋白和mRNA表达在缺氧2h开始升高（P〈0．05），并持续至缺氧8h（P〈0．01）：细胞线粒体丰富。核糖体及粗面内质网逐渐增多。结论 缺氧可能在基因转录水平诱导VEGF表达，后者通过自分泌途径刺激cAVM血管内皮细胞增殖。     

Heart rate and heart rate variability changes in the intracarotid sodium amobarbital test

PURPOSE: Changes in heart rate and heart rate variability have been found in prior studies performed during the intracarotid sodium amobarbital (ISA) test. However, these results are not entirely consistent with current models of differential cerebral involvement in the modulation of the heart. This study was designed to re-investigate this topic with a larger N than has heretofore been used. METHODS: The electrocardiogram was recorded during left and right ISAs in 73 subjects. Raw heart rate and heart rate variability were calculated. RESULTS: Raw heart rate increased during inactivation of either hemisphere, but more so for the right hemisphere. Heart rate variability changes consistent with decreasing parasympathetic tone also were found to occur during either ISA, but to a significant degree, only during right ISA. CONCLUSIONS: The right hemisphere appears to have a greater role in cerebral regulation of cardiac function, perhaps by virtue of the modification of parasympathetic effects.     

A Capitated Model for a Cross-Section of Severely Mentally Ill Clients: Employment Outcomes

Employment outcomes are examined in a three year controlled study of two Integrated Service Agencies (ISAs) for a cross-section of severely mentally ill clients. At each site significantly more ISA members than comparison clients obtained some paid employment. At the urban site the difference was dramatic: 73 vs 15 percent worked during the study period, and 29 percent of the ISA clients worked competitively. The significant but still limited ISA results argue for increased employment opportunities for all seriously mentally ill clients.     

VEGF mRNA Induction Correlates With Changes in the Vascular Architecture Upon Spinal Cord Damage in the Rat

The multiple cellular and molecular processes induced by injury to the central nervous system (CNS) are still poorly understood. In the present study, we investigated the response of the vasculature and the expression of mRNA for the angiogenic vascular endothelial growth factor (VEGF) following X-irradiation of the spinal cord in the newborn and following traumatic spinal cord injury in the adult rat. Both lesion models induced changes in the density and the distribution pattern of blood vessels: while X-irradiation led to a permanent local increase in vascular density in the fibre tracts of the exposed segments, a transient local sprouting of vessels was induced upon traumatic spinal cord injury. In situ hybridization showed that an increase of VEGF mRNA anticipated and overlapped with the vascular responses in both lesion models. In addition to the temporal correlation of VEGF expression and vascular sprouting, there was a clear correlation in the spatial distribution patterns. Following X-irradiation, the expression of VEGF mRNA was restricted to the fibre tracts, precisely the areas where the changes in the vasculature were observed later on. Upon transection in the adult animal, VEGF was mainly detectable at the border of the lesion area, where the transient increase in vascular density could be observed. Interestingly, according to the type of lesion applied, astrocytes (X-irradiation) or inflammatory cells (presumably microglial cells or macrophages; traumatic lesion) are the cellular sources of VEGF mRNA. Our results strongly indicate that VEGF is crucially involved in mediating vascular changes following different types of injury in the CNS.     

A Capitated Model for a Cross-Section of Severely Mentally Ill Clients: Hospitalization

Hospitalization outcomes are examined in a threeyear random assignment controlled study of two capitatedIntegrated Service Agencies (ISAs) in California. Studyparticipants were a cross-section of severely mentally ill clients. Using the flexibility ofcapitated funding, the urban ISA reduced inpatientlength of stay and days, but not admissions. Elements ofthe capitated ISA model worked together to produce clinically appropriate and less costly use ofinpatient services. At the rural ISA, admissions werereduced substantially during the first two years of thedemonstration but not costs.     

What about the patient?

Our mental health care system fails to serve the very people whose suffering that system ostensibly exists to alleviate. This article relates the stories of 3 people who fell through the cracks of this system. An alternative approach, the Integrated Services Agency (ISA), has been implemented in California and offers hope to persons with schizophrenia. The ISA approach focuses on the expressed needs of the members it exists to serve, and both members and staff have experienced changes in their roles and expectations. Staff and members have learned that engagement with the "outside world" involves taking risks but that risk avoidance only perpetuates the status quo. The ISA approach rewards growth and patients' being well rather than rewarding docility and illness. Medication is neither ordered nor assigned, but chosen in a collaboration between staff and members. ISAs have returned care to the mental health care system.     

VEGF在人脑胶质瘤中的表达与肿瘤增殖及肿瘤血管生成的关系

目的研究血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)在人脑胶质瘤中的表达与肿瘤增殖及血管生成的关系。方法应用免疫组化技术和形态定量分析法,检测98例手术切除脑胶质瘤中VEGF表达、PCNA标记指数(PCNA LI)、微血管密度(Microvessel density,MVD)表达。结果(1)肿瘤细胞及血管内皮细胞均可以表达VEGF,阳性颗粒分布于肿瘤胞浆中;(2)高级别肿瘤PCNA、LI、MVD显著高于低级别肿瘤(P<0.05);VEGF表达阳性肿瘤的PCNA、LI、MVD显著高于VEGF表达阴性肿瘤(P<0.05);(3)在星形细胞肿瘤中,随着MVD的增大,VEGF在肿瘤血管内皮的染色率逐渐增加,与肿瘤的MVD存在正相关关系(r值为0.44,P<0.01)。结论脑胶质瘤的VEGF表达与MVD呈正相关关系,VEGF在肿瘤细胞增殖及血管再生过程中起重要作用。     

Expression of vascular endothelial growth factor (VEGF) in rat brain after subarachnoid haemorrhage and endothelin receptor blockage with BQ-123

Cerebral vasospasm is one of the most severe complications of subarachnoid haemorrhage (SAH), leading to pathological changes in the vessel wall itself and in the nervous tissue, due to ischaemia of endothelial cells and neurones. Amongst the known substances inducing vasospasm, the most potent spasmogenic effect is exerted by endothelin-1 (ET1). The constriction of cerebral arteries and obliteration of capillaries highly stimulates the secretion of growth factors by endothelial cells and induces compensatory formation of collateral circulation in response to brain ischaemia. Expression of vascular endothelial growth factor (VEGF), the main factor responsible for angiogenesis and vascular permeability, was found to be increased in hypoxic cells (irrespective of the cause of hypoxia) as well as in neoplastic cells in the brain. The aim of the study was to determine whether chronic vasospasm and hypoxia of endothelial cells stimulate expression of VEGF, and whether blockage of the endothelin receptor ET(A) reduces this expression. The SAH was induced experimentally in male Wistar rats and the ET(A) receptor antagonist--BQ-123 was administered into the cisterna magna. After 48 hours the brain was removed and expression of VEGF studied immunohistochemically on paraffin sections. We found that hypoxia of endothelial cells, induced by chronic vasospasm after SAH, caused increased expression of VEGF in brain vessels and neurones of the cerebral hemispheres, brain stem and cerebellum. After administration of the endothelin receptor antagonist BQ-123, no changes in VEGF expression in the brain were found.     

Brain-specific expression of vascular endothelial growth factor 146 correlates with the blood-brain barrier induction in quail embryos

Homeostasis of the neural environment is indispensable for the normal functioning of neural cells, and is maintained by the blood-brain barrier (BBB). The BBB is induced during embryonic development. The present study aimed to clarify the molecular mechanisms of BBB induction in neural tissues. Using an in vivo model of BBB induction that is based on xenograft transplantation between quail and chick embryos, we showed that the gene expression in developing brain cells is appropriately regulated to generate the neural microenvironment for endothelial cells to form the neural tissue-specific vascular structure with a BBB function. Vascular endothelial growth factor (VEGF) is a factor controlling vascular proliferation as well as vascular permeability, and is known to be produced by developing brain cells. In the present study, we show that the isoforms of VEGF produced by developing quail brain cells change with close temporal correlation to the BBB induction. Among four isoforms, VEGF(122) and VEGF(166) were expressed constitutively during the course of embryonic development, while the expressions of VEGF(146) and VEGF(190) were upregulated after the differentiation of endothelial cells to BBB-forming cells had begun. Furthermore, through investigation into developing extracranial tissues, the changes in VEGF isoform expression, especially the upregulation of VEGF(146) expression, were shown to be specific for brain tissues that contain the blood vessels with BBB properties. These results suggest that the expression of VEGF isoforms by brain cells is developmentally regulated for the achievement of brain development including the BBB induction.     

缺血再灌注对鼠脑血管内皮生长因子表达的影响

目的 了解血管内皮生长因子（VEGF）在一过性全脑缺血再灌注鼠脑表达的动态变化。方法 采用Pulisnelli改良法四血管堵塞全脑缺血再灌注模型,用免疫组织化学方法观察了全缺血15min再灌注2－14d时,VEGF表达的动肪变化。结果 全脑缺血15min再灌注6h VEGF即可在大脑皮层,纹状体及丘脑等区域的血管内皮细胞表达,1d达高峰,一直持续到缺血后再灌注3d,结论 脑缺血后再灌注可上调VEGF在大脑皮质,纹状体及丘脑等区域内皮细胞的表达,VEGF可能通过促进血管内皮细胞生长对缺血性神经元损伤起一定的作用。     

脑膜瘤组织VEGF／VPF、KDR的表达及意义

目的研究脑膜瘤血管生成及瘤周脑水肿与VEGF/VPF及其受体KDR的关系。方法采用Northern印迹分子杂交和免疫组化技术检测47例脑膜瘤组织VEGF/VPFmRNA、VEGF/VPF和KDR蛋白表达,分析其与微血管密度(MVD)和瘤周脑水肿度DPTBE的关系。结果47例脑膜瘤均表达4.2Kb的VEGF/VPFmRNA片段,VEGF/VPF蛋白表达与其mRNA的表达一致,80.9%的肿瘤KDR蛋白表达阳性,VEGF/VPF和KDR分别定位于脑膜瘤瘤细胞和血管内皮细胞胞浆。VEGF/VPFmRNA表达与脑膜瘤MVD和DPTBE呈正相关r=0.67,P<0.01r=0.54,P<0.01;KDR阳性组脑膜瘤VEGF/VPFmRNA表达水平、MVD、DPTBE均显著高于KDR阴性组(P<0.01)。结论脑膜瘤细胞可产生VEGF/VPF,通过KDR介导促肿瘤血管生成和增加血管通透性,在脑膜瘤瘤周脑水肿的发生发展过程中起重要作用。