细胞间粘附分子1及其抗体与脑血管痉挛

SAH后CVS的发生和发展是受痉挛血管周围的血液刺激启动的,这包括血管内皮细胞功能的紊乱。痉挛血管内皮细胞壁上有明显的ICAM-1的上调,且与血管的痉挛程度密切相关。ICAM-1介导白细胞粘附到血管内皮细胞,并透过内皮屏障迁移到组织中。ICAM-1介导的血管壁的炎症反应在SAH后CVS的病理生理过程中起了重要作用,而应用抗ICAM-1单克隆抗体进行治疗可以有效缓解CVS的程度。     

颅脑损伤后细胞间粘附分子-1的变化及临床意义

细胞间粘附分子-1（ICAM-1）是由内皮细胞表达,介导白细胞-内皮细胞粘附的重要分子之一。颅脑损伤后脑血管内皮细胞表面ICAM-1迟发表达增强,使白细胞局部聚集,阻塞微循环,同时激活的白细胞释放大量炎性因子,进一步加重脑微循环障碍及血脑屏障损害,导致继发性脑损伤。了解颅脑损伤后后ICAM-1的变化规律,可为临床提供新的病情检测指标及治疗途径。     

脑梗死患者急性期可溶性粘附分子的变化及临床意义

目的:为了解脑梗死患者急性期可溶性粘附分子的变化及临床意义。方法:采用双抗体夹心ELIsA法测定76例脑梗死患者血清sICAM-1、sVCAM-1、sE-selectine,并与52例TIA患者和40例健康老年人对照比较。结果:脑梗死患者24小时内血清sICAM-1、sVCAM-1、sE-selectine水平明显高于TIA和健康对照组(P<0.01)。大梗死灶组血清sICAM-1、sVCAM-1、sE-selectine水平明显高于中梗死灶组和小梗死灶组。脑梗死患者血清sICAM-1、sVCAM-1、sE-selectine水平在脑梗死发生24小时至7天呈现上升趋势,7天至14天呈下降趋势。结论:sICAM-1、sVCAM-1、sEselectine与急性脑梗死密切相关,参与了缺血后脑组织损伤的病理过程。在脑梗死急性期阻断粘附分子的表达可能有助于减轻缺血性脑损伤。     

急性脑梗死血清可溶性细胞间粘附分子的变化及意义

目的为了解急性脑梗死患者血清可溶性细胞间粘附分子（sICAM-1)的变化及临床意义。方法采用双抗体夹心ELSA法测定了68例脑梗死患者血清sICAM-1,并与31例TIA患者和30例正常人对照比较。结果脑梗死患者24小时内血清sICAM-1水平明显高于TIA和正常对照组(P<0.01)。大梗死灶组血清sICAM明显高于中梗死灶组和小梗死灶组。脑梗死患者血清sICAM-1水平在脑梗死发生24小时至7天呈现上升趋势,7至14天呈下降趋势。结论sICAM-1与急性脑梗死密切相关,参与了缺血后脑组织损伤的病理过程。实验证明,急性脑梗死早期大量白细胞聚集阻塞微血管,穿越内皮细胞进入组织,使局灶区组织受损。此时白细胞聚集与sICAM-1表达增强密切相关。     

脑血管病患者细胞间粘附分子—1的测定及意义

目的：探讨脑血管病患者血清细胞间粘附分子－１（ＩＣＡＭ－１）水平和脑血管病发病与治疗的关系。方法：用ＥＬＩＳＡ法测定脑血管病患者和正常对照组血清可溶性细胞间粘附分子－１（ｓＩＣＡＭ－１）含量。结果：脑血栓形成或脑出血患者血清ｓＩＣＡＭ－１含量均较对照组显著增高（Ｐ〈０．０１;Ｐ〈０．０１）;Ⅲ伴有高血压的脑血栓形成、脑出血患者血清ｓＩＣＡＭ－１含量较正常血压者显著增高（Ｐ〈０．０５）。结论：ＩＣＡ     

氦氖激光治疗偏头痛及血清细胞间粘附分子—1的监测

对 38例偏头痛患者进行低能量氦氖激光治疗 ,疗效明显 ,同时治疗前后抽血测定血清可溶性细胞间粘附分子(ICAM- 1) ,探讨激光治疗偏头痛的机制。1　资料与方法偏头痛组 :选择门诊偏头痛患者 38例 (排除紧张性头痛 ) ,男 2 0例 ,女 18例 ,年龄 30～ 5 7岁 ,平均 42 .7岁。均符合WHO头痛分类专门委员会 196 2年制定的偏头痛标准和1988年国际头面部疼痛分类标准 [1 ]。无高血压、直立性低血压、心脑血管疾病 ,无精神病史。正常对照组 30例 ,均为无疼痛病史的健康献血者 ,男 12例 ,女 18例 ,年龄 2 8～ 48岁 ,平均 38.5岁。低能量氦氖 (He- N…     

脑缺血抗细胞间粘附分子—1抗体作用的实验研究

目的探讨抗细胞间粘附分子－１（ＩＣＡＭ－１）抗体保护神经元缺血性损伤的作用机制。方法分离培养鼠脑毛细血管内皮细胞（ＣＣＥＣ）和多形核白细胞（ＰＭＮ），利用微管吸吮技术，观察ＰＭＮ与ＣＣＥＣ间粘附力学特性的变化。结果脑缺血－再灌注后各时间点，ＰＭＮ与ＣＣＥＣ的粘附力和粘附应力均明显高于正常对照组和伪手术组（Ｐ＜０．０１）；加抗ＩＣＡＭ－１抗体后，细胞粘附力和粘附应力均明显下降（Ｐ＜０．０５或Ｐ＜０．０１）。结论脑缺血－再灌注损伤后抗ＩＣＡＭ－１抗体使ＰＭＮ与ＣＣＥＣ粘附力减小，粘附应力下降；抗粘附分子抗体将可能成为治疗缺血性脑血管疾病的一条新的有效途径     

高血压性脑出血后细胞间粘附分子-1的表达与白细胞浸润的关系

高血压性脑出血后出血部位及血肿周围脑组织存在着炎性反应，是脑出血后病理生理机制的重要环节，其炎性反应的重要标志就是白细胞在局部的粘附聚集，而介导白细胞浸润的重要的细胞因子就是细胞间粘附分子-1（ICAM-1）。探讨高血压性脑出血后ICAM-1的表达与白细胞浸润的关系，并据此制定合理有效的治疗方案，对于降低脑出血的死亡率，提高生存质量十分重要，本文对此关系综述如下。     

急性吉兰-巴雷综合征患者血清及脑脊液转化生长因子-β1和可溶性细胞间粘附分子-1的变化

近年来研究表明 ,吉兰 巴雷综合征 (Ｇｕｉｌｌａｉｎ Ｂａｒｒ啨ｓｙｎｄｒｏｍｅ,ＧＢＳ)的发病与免疫细胞因子等的异常变化密切相关。我们于 1996年 2月至 1998年 12月间对急性ＧＢＳ患者血清和脑脊液转化生长因子 β1(ＴＧＦ β1)和可溶性细胞间粘附分子 1(ｓＩＣＡＭ 1)水平进行了研究 ,旨在探讨上述两种细胞因子在ＧＢＳ发病中的作用。资料 :( 1)急性ＧＢＳ组 :3 8例 ,男 2 2例 ,女 16例 ,年龄 15～ 5 9岁 ,平均 2 3 5岁 ,均系我院门、急诊及住院患者 ,所有患者的诊断符合Ａｓｂｕｒｇ1990年修订的诊断标准。 ( 2 )非炎症性神经病 (…     

脑血管病患者细胞间粘附分子-l的测定及意义

目的探讨脑血管病患者血清细胞间粘附分子-1(ICAM-1)水平和脑血管病发病与治疗的关系。方法用EUSA法测定脑血管病患者和正常对照组血清可溶性细胞间粘附分子-1(Sicam-1)含量。结果脑血栓形成或脑出血患者血清Sicam-1含量均较对照组显著增高(P<o．01;P<o．01);伴有高血压的脑血栓形成、脑出血患者血清Sicam-1含量较正常血压者显著增高(p<o．05)。结论ICAM-1在高血压引起脑卒中发病及治疗方面具有重要意义。     

T细胞亚群及粘附分子在实验性变态反应性神经炎中的作用

目的探讨Ｔ细胞亚群及粘附分子在实验性变态反应性神经炎（ＥＡＮ）中的作用。方法用兔坐骨神经匀浆免疫Ｗｉｓｔａｒ大鼠，建立ＥＡＮ模型；同时用抗细胞间粘附分子－１（ＩＣＡＭ－１）单抗注入大鼠后再诱导ＥＡＮ。观察自然病程组、抗体注射组及对照组动物的临床病理。用双重酶标免疫组化技术检测ＣＤ４＋、ＣＤ８＋Ｔ细胞分布以及粘附分子ＣＤ５４、ＣＤ１１ａ、ＣＤ６２在ＣＤ４＋及ＣＤ８＋细胞上的表达。结果抗体注射组发病率及发病程度明显低于自然病程组；组织中粘附分子在ＣＤ４＋细胞上的表达及ＣＤ４＋／ＣＤ８＋自然病程组高于抗体注射组；ＣＤ５４、ＣＤ１１ａ在ＣＤ４＋细胞上的表达高于ＣＤ８＋细胞。结论ＣＤ４＋细胞是主要的效应细胞，ＣＤ４＋细胞上粘附分子的表达对效应Ｔ细胞进入病变组织起主导作用；抗ＩＣＡＭ－１抗体能够预防ＥＡＮ发生。     

Influence of gangliosides on experimental allergic neuritis

The development of myelin-induced experimental allergic neuritis (EAN) in Lewis rats can be depressed and delayed by adding a ganglioside mixture (GM1, GD1a, GD1b, GT1b) to the immunization compound; however, gangliosides may enhance the induction of adjuvant arthritis. Antibodies against multiple gangliosides are produced in rats after immunization with gangliosides after addition of myelin, but only low titers can be detected in animals immunized with myelin and complete Freund's adjuvant alone. We conclude that this antibody production is not the result of peripheral nerve inflammation but depends rather from external applied gangliosides.     

Elevated soluble intercellular adhesion molecules-1 in inflammatory myopathy

Introduction – We evaluated the serum level of soluble intercellular adhesion molecule-1 (sICAM-1) in patients with polymyositis (PM) and dermatomyositis (DM) and investigated the correlation between the serum level of sICAM-1 and clinical findings. Material and methods – We measured the serum level of sICAM-1 using an enzyme-linked immunosorbent assay in 19 untreated patients with inflammatory myopathy (14 patients with PM and 5 patients with DM), 20 patients with other neuromuscular disorders in which immunological mechanisms are unlikely to be involved, and 14 normal healthy controls. Results – The serum level of sICAM-1 was significantly higher in patients with PM/DM compared with patients with other neurological disorders and control subjects. The sICAM-1 level was, however, not correlated with the clinical characteristic including disease severity, the duration of illness, and the serum level of CK. Conclusion – These findings suggest that sICAM-1 is involved in the inflammatory process of PM and DM.     

Demyelination produced by experimental allergic neuritis serum and anti-galactocerebroside antiserum in CNS cultures

Summary Cultures of mouse cerebellum were exposed to sera from rabbits with experimental allergic neuritis induced by whole peripheral nerve immunization (WN-EAN) and to rabbit anti-galactocerebroside (GC) antisera, and were studied by electron microscopy. Both antisera produced almost identical demyelinative patterns. These consisted of large intramyelinic splittings, smudged changes of myelin, degeneration of oligodendrocytes, and phagocytosis of myelin by astrocytes, changes similar to those described after application of whole spinal cord-induced experimental allergic encephalomyelitis (WM-EAE) sera. In addition, patterns which have been considered more characteristic of in vivo demyelinative lesions have been found, such as vesicular disruption of myelin lamellae and peeling off and phagocytosis of myelin by phagocytic mononuclear cells with electron dense cytoplasm. The morphologic similarities between demyelinative patterns in central nervous system (CNS) cultures induced by anti-GC antiserum and WN-EAN serum and WM-EAE serum, and the fact that elevated antibody titers to GC are found in sera from rabbits with WN-EAN and WM-EAE (Saida, et al., 1977), support the concept that anti-GC antibody is the major factor in the production of CNS demyclination in vitro by sera from rabbits with WN-EAN and WM-EAE.This work was supported by grants from the National Institute of Health NS 11037-05, the National Multiple Sclerosis Society 894-B, and the Kroc Foundation     

Biphasic form of experimental autoimmune neuritis in dark Agouti rats and its oral therapy by antigen-specific tolerization

A new and biphasic form of experimental autoimmune neuritis (EAN) is described in dark agouti rats (DA rats) and is inducible by a single immunization with bovine peripheral nerve myelin (BPM) in complete Freund's adjuvant (DA-EAN). Animals develop a mild episode of disease; after recovery, 66-100% of the rats suffer from a more severe bout of EAN with paraparesis 25-30 days after immunization. By histology, DA-EAN is an inflammatory and demyelinating polyradiculoneuropathy virtually without axonal damage. Demyelination affects mainly spinal roots. This is also reflected by markedly increased F-wave latencies in nerve conduction studies of sciatic nerves. In sciatic nerves, inflammation and demyelination are found only focally and may be the histopathologic basis for conduction failure in some fibers. Immunologic investigations revealed stronger proliferative responses of DA than of Lewis rat lymph node cells to BPM and various peptides derived from the P2 protein. Proliferative and Th1-cytokine responses were particularly pronounced in spleen during the late phase of DA-EAN as compared to the monophasic EAN of Lewis rats. The data suggest that persistent lymphocyte proliferation with secretion of interferon (IFN)-gamma may be relevant for the relapsing course of DA-EAN whereas epitope spreading may explain the increased severity of the second bout of disease. The extended Th1 response in DA rats did not go along with a lack of downregulatory mechanisms, because the second DA-EAN attack was self-limited and splenocytes from DA rats produced considerable amounts of interleukin (IL)-10 and transforming growth factor (TGF)-beta. To substantiate further a functional immunoregulation in DA rats, we modulated DA-EAN by antigen-specific oral tolerization, which is known to involve active suppressor mechanisms. Preventive feeding of BPM in combination with cholera toxin (CT) induced a long-lasting resistance to DA-EAN. Even therapeutic administration of BPM or BPM/CT after onset of signs of disease significantly mitigated the further course of disease and prevented development of paraparesis. Because DA-EAN is easily inducible and leads consistently to relapses in most rats, it can be used for studies of immune factors that determine a relapsing course of autoimmunity. Furthermore, DA-EAN may serve as a model for relapsing inflammatory demyelinating polyneuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) and for treatment studies. Our findings on effective prevention and therapy of DA-EAN by oral application of myelin/CT corroborate this form of immunomodulation as a treatment strategy for cell-mediated processes in chronic inflammatory neuropathies.     

Role of intramuscular enzymatic changes in the development of muscular weakness in rats with experimental allergic neuritis

We investigated the role of intramuscular enzymatic changes in the development of muscular weakness in rats suffering from experimental allergic neuritis. At an initial stage without apparent clinical symptoms, enzymatic changes of similar types occurred in the muscles of the forelimbs and hind limbs. At a later stage when the weakness appeared in the hind limb but not in the forelimb, dissociation of the pattern of the enzymatic changes occurred between the two limbs. Comparison of the intramuscular enzymatic changes between the two stages and between the two limbs suggested that the increased activities of aminopeptidases and endopeptidases play some important roles in the development of muscular weakness in this experimental model. Low molecular weight protease inhibitors may thus be worthy of a trial in this disease condition.     

Adhesion molecule expression in experimental myositis

Experimental allergic myositis (EAM) in Lewis rats, induced with partially purified myosin, is regarded as a model of human polymyositis. To clarify the role of adhesion molecules in the pathogenesis of EAM in Lewis rats, we investigated intramysial expressions of the intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, and the serum level of soluble ICAM-1 in EAM rats. All the EAM rat muscles had scattered inflammatory foci, as well as cell infiltration and necrosis, by week 4 after the initial immunization (i.e., day 0 after the last immunization). As compared with the control muscles, ICAM-1 and VCAM-1 were strongly expressed immunohistochemically in the endothelium of vessels in the endomysium and perimysium, and to lesser extents in the inflammatory infiltrates and on the sarcolemma of nonnecrotic muscle fibers adjacent to the inflammatory infiltrates or invaded muscle fibers. ICAM-1 in the muscle extracts and sera from EAM rats increased on each test day, as compared with extracts from the normal controls. The values peaked on day 0 after the last immunization, then gradually decreased with time. ICAM-1 elevations in the muscle extracts were correlated with the percent of sections that had inflammatory lesions (P = 0.032) and the histological scores (P = 0.005) on day 0, whereas there was no significance on days 3 and 7. These findings suggest that the adhesion molecules ICAM-1 and VCAM-1 increase in the early stage of EAM, and function in the initiation of the inflammatory process of myositis.     

单核细胞趋化蛋白-1和调节活化正常T细胞表达分泌因子与实验性变态反应性神经炎的关系

目的 研究趋化因子单核细胞趋化蛋白-1（MCP-1）和调节活化正常T细胞表达分泌因子（RANTES）与实验性变态反应性神经炎（EAN）发病的关系，探讨EAN的免疫发病机制。方法 给Wistar大鼠足垫皮下注射兔坐骨神经匀浆建立EAN模型，用免疫组化技术检测EAN大鼠发病不同时间坐骨神经MCP-1和RANTES的表达。结果 EAN组的MCP-1表达第9d达高峰，随后逐渐下降，第15d、21d、28dMCP-1的表达与前一时间点比较差异均有显著性（均P〈0．01）；第9d、15d、21dMCP-1表达均显著高于对照组（均P〈0．001）。EAN组第9d、15d、21dRANTES表达均显著高于对照组（P〈0．01～0．001），第15d表达最高。结论 MCP-1和RANTES在EAN的发病过程中发挥了重要作用，MCP-1可能起始动作用，RANTES可能与EAN的病情进展有关。