蛔虫变应原诱发豚鼠哮喘后血液流变学及组织胺动态变化

目的 :为了观察蛔虫变应原致喘豚鼠动物模型后血液流变学变化及外周血组织胺的动态变化 ,丰富变应原激发动物哮喘的基础理论。方法 :把实验豚鼠随机分为阴性对照组、佐剂对照组和阳性激发组。用蛔虫变应原激发致喘豚鼠后 ,观察各实验组在激发哮喘后 1h、 2 4h和 72h的血液流变学和组织胺的动态变化。结果 :由蛔虫变应原引起的过敏性哮喘豚鼠动物模型 ,其血液流变性出现异常 ,阳性激发组的血浆粘度、红细胞聚集指数、全血高切变率还原粘度和组织胺水平均较阴性对照组、佐剂对照组显著性升高 (P <0 .0 1) ;而红细胞压积则无明显变化。结论 :表明用蛔虫变应原致喘豚鼠后 ,能诱发速发型变态反应 ,导致肥大细胞和嗜碱性粒细胞脱颗粒并释放出组织胺。与此同时血液出现高粘滞状态 ,进一步加剧气道局部的缺血、缺氧及炎性反应 ,导致气体交换障碍、肺功能降低。     

泽兰对家兔血液流变性及球结膜微循环的影响

观察泽兰水煎剂对家兔血液流变性及微循环的影响。实验结果表明，腹腔注射泽兰１ｇ／ｋｇ（体重），对全血比粘度、血浆比粘度、红细胞压积和全血还原粘度均有明显降低作用（Ｐ＜０．０１～０．０５），红细胞电泳时间缩短（Ｐ＜０．０１）。体外血栓形成实验表明，泽兰能够缩短血栓长度，减轻血栓干、湿重（Ｐ＜０．０１）。腹腔注射泽兰０．５ｇ／ｋｇ，可见功能毛细血管开放增加（Ｐ＜０．０１），也能改善高分子右旋糖酐所致急性微循环障碍     

住院治疗男性冠心病患者血液流变性变化的特点

２８例男性住院治疗冠心病（ＣＨＤ）患者，接受１０～４０天流变药物的治疗，虽然患者比积明显低于对照组（Ｐ＜０．０５），而血浆粘度明显高于对照组（Ｐ＜０．０１），但患者表观全血粘度及红细胞聚集指数与对照组无显著区别。若采用固定比积（０．５０）的红细胞ＰＢＳ，悬液，患者血样的表观粘度则明显高于对照组（Ｐ＜０．０５或＜０．０１）；红细胞聚集指数也明显高于对照组（Ｐ＜０．０５）。结果表明，红细胞变形性明显减弱和聚集性显著升高是住院男性冠心病患者血液流变性异常的主要特点，并提示，改善红细胞流变性异常和降低血浆粘度对冠心病患者可能是一种有益的治疗措施。     

糖尿病肾病与血液粘度

为研究糖尿病肾病患者血液粘度的改变，对不同病程度的糖尿病肾病患者血液粘度进行了观察。结果显示，大量白蛋白尿组患者高切变率（２４０ｓ－１）和低切变率（４８ｓ－１全血粘度增多明显低于正常白蛋白尿组（Ｐ＜００５，Ｐ＜００１），其红细胞压积也显著低于正常白蛋白尿组（Ｐ＜００１）。微量白蛋白尿组血液粘度和红细胞压积与正常白蛋白尿组比较均无显著差异。提示糖尿病肾病患者随病程进展出现肾性贫血而致红细胞压积减小，全血粘度降低。抗凝剂的使用也是影响血液粘度的因素之一     

新鲜羊膜致Ⅰ型超敏反应的变应原性研究

研究新鲜人羊膜的变应原性及其致敏后发生Ⅰ型超敏反应的可能性。建立豚鼠全身主动过敏实验模型。分新鲜羊膜组、新鲜蛋清组（阳性对照）和PBS液组（阴性对照），每组10只豚鼠。观察豚鼠在致敏期和激发后的反应，采用化学荧光法检测外周血组胺含量，血液流变分析系统检测4项血液流变学指标（全血高切变率黏度、全血低切变率黏度、血浆黏度、红细胞聚集指数）。致敏期间各组豚鼠的体重变化无明显差别（P〉0．05）；激发后羊膜组豚鼠与阴性组表现一致，无异常反应；羊膜组外周血组胺含量及4项血液流变学指标均与阴性对照无明显差别（P〉0．05），与阳性对照有显著性差异（P〈0．01）。经规范化无菌处理后的新鲜羊膜，一般不具有变应原性，不会引起Ⅰ型超敏反应。     

896例脑血栓患者血液流变性分析

检测８９６例脑血栓患者血液流变性九项指标，结果发现其均明显高于８０８例对照组（Ｐ＜０．０５或＜０．０１）。以红细胞流变性改变为基础，分为正常型、全高型、高粘型、高聚型及高压积型。血液流变性的异常是脑血栓发病的重要因素。粘度越高，脑血流量越低；压积越高，粘度越大；ＲＢＣ表面电荷越少，聚集性越强。提示：血液流变学检测的意义在于阐明发病机理、指导临床治疗、帮助患者康复。     

体外反搏对血液流变性和血小板聚集性的影响

观察４０例心脑血管疾病患者体外反搏前后血液流变性和血小板聚集性变化。结果表明，反搏后全血比及还原比粘度、血浆粘度有不同程度的下降（Ｐ＜０．０５～０．０１）。反搏治疗后，１～５ｍｉｎ血小板聚集率、最大聚集率和最大聚集速度较反搏前均明显降低（Ｐ＜０．０５～０．０１），而５ｍｉｎ解聚率则明显增加（Ｐ＜０．０５）。提示体外反搏治疗不仅影响血液动力学，而且明显降低血液粘度，对血小板聚集功能有明显抑制作用。     

肺结核患者血液流变学指标的观察

３１例肺结核病患者的血液流变学指标检测结果显示８７．１％（２７例）的患者同时伴有高粘滞血症，其血液流变性有异常变化，特别是全血粘度、血浆粘度、红细胞聚集性、红细胞变形性和血液屈服应力等结果均有显著改变（Ｐ＜０．０１。提示：在肺结核病的诊疗中，及时检测患者的血液流变性，对该病的诊治、病情观察、验证药效及预后等均有重要意义。     

新鲜羊膜致I型超敏反应的变应原性研究

研究新鲜人羊膜的变应原性及其致敏后发生I型超敏反应的可能性。建立豚鼠全身主动过敏实验模型。分新鲜羊膜组、新鲜蛋清组(阳性对照)和PBS液组(阴性对照),每组10只豚鼠。观察豚鼠在致敏期和激发后的反应,采用化学荧光法检测外周血组胺含量,血液流变分析系统检测4项血液流变学指标(全血高切变率黏度、全血低切变率黏度、血浆黏度、红细胞聚集指数)。致敏期间各组豚鼠的体重变化无明显差别(P>0.05);激发后羊膜组豚鼠与阴性组表现一致,无异常反应;羊膜组外周血组胺含量及4项血液流变学指标均与阴性对照无明显差别(P>0.05),与阳性对照有显著性差异(P<0.01)。经规范化无菌处理后的新鲜羊膜,一般不具有变应原性,不会引起I型超敏反应。     

家兔血液流变学参数及其影响因素

目的检测正常家兔血液流变学指标,建立其正常参考值,并对有关影响因素进行探讨。方法采用ＮＸＥ－１型锥板式粘度计。测定５．７５５~(－１)～３０７．２Ｓ~(－１)七个切变率的血液表观粘度、血浆粘度、红细胞硬度指数（ＴＫ）、红细胞聚集指数（ＲＡＩ）和氧释放系数（ＯＤ）。结果雄性组家兔高切变率和低切变率下的血液粘度及ＲＡＩ较雌性组明显增高（Ｐ<０．０５和Ｐ<０．０１）,而ＯＤ较雌性组明显降低（Ｐ< ０．０５）。高体重组家兔高、中、低各切变率下的血液粘度和红细胞压积（Ｈｃｔ）较低体重组明显增高（Ｐ< ０．０５和Ｐ<０．０１）,而ＯＤ明显低于低体重组（Ｐ<０．０５）。高Ｈｃｔ组家兔的血液粘度、ＯＤ较低Ｈｃｔ组明显增高（Ｐ均<０．０１）,而血浆粘度和ＴＫ较低Ｈｃｔ组明显降低（Ｐ＜０．０５和Ｐ<０．０１）。结论家兔不同性别、体重和Ｈｃｔ,其血液流变学指标存在明显差异。     

Changes in airway responsiveness and β- and α-adrenergic receptors in the lungs of guinea pigs with experimental asthma

The effects of inhaled allergen on airway responsiveness and on beta- and alpha-1-adrenergic receptors on lung membrane were investigated in guinea pigs. After measuring the respiratory threshold to histamine (RT-HIS), one group of guinea pigs passively sensitized for ovalbumin was challenged by allergen inhalation (challenged group). Measurement of the RT-HIS 24 h following challenge revealed a significant decrease from 687 micrograms/ml (mean, n = 16) to 407 micrograms/ml (P less than 0.05). In addition the RT-HIS 24 h after challenge was also significantly lower in the challenged group than in controls (n = 9, P less than 0.05). The density of beta-adrenergic receptors on the lung membrane of the challenged group was 594 +/- 32 (mean +/- SE) fmol/mg protein (n = 11) compared with 712 +/- 24 fmol/mg protein (n = 9) in the controls, a statistically significant difference (P less than 0.05). A significant correlation was found between the RT-HIS and density of beta-adrenergic receptors. From these results, we concluded that the exaggerated airway responsiveness 24 h after allergen challenge is in part due to a decrease in the density of beta-adrenergic receptors. There was no difference in the density of alpha-1-adrenergic receptors nor a significant correlation between the RT-HIS and the number of alpha-1-adrenergic receptors in the challenged vs. the control groups.     

艾蒿花粉诱导豚鼠过敏反应

目的：研究艾蒿花粉粗提物（MPE）和其主要成分之一artemisia vulgaris 1（Art V1）能否诱导豚鼠过敏反应,为艾蒿花粉过敏症研究建立动物模型。方法: 艾蒿花粉粗提物或Art V1混悬于佐剂氢氧化铝凝胶中,每间隔10 d致敏豚鼠1次,共4次,然后以艾蒿花粉粗提物或Art V1抗原滴鼻诱发鼻炎症状。气道高反应性(AHR)、炎症细胞和肺组织病理的观察于Art V1气雾攻击5 d后,以乙酰甲胆碱（Mch）气雾吸入激发AHR,测定气道阻力和动态肺顺应性,计数和分类计数支气管肺泡灌洗液（BALF）中的炎症细胞,观察肺组织病理学改变。 结果: Art V1组豚鼠在抗原激发下喷嚏次数和抓鼻次数显著增加,吸入Mch后气道阻力明显增加,动态肺顺应性明显降低,Mch气雾吸入可激发AHR;MPE组豚鼠喷嚏次数有所增加,气道反应性有所升高;两组BALF和病理切片均显示明显的嗜酸性粒细胞和中性粒细胞浸润。结论: 艾蒿花粉粗提物和其主要成分Art V1均能诱导豚鼠过敏反应,Art V1致敏效果明显优于艾蒿粗提物。该模型的建立有利于过敏性疾病机制和治疗新药的研究。     

The tryptase inhibitor APC-366 reduces the acute airway response to allergen in pigs sensitized to Ascaris suum

BACKGROUND: Tryptase is a mast cell serine protease that is released during mast cell degranulation. It has been implicated as an important enzyme in the pathophysiology of asthma, but its role in this disease is not fully elucidated. OBJECTIVE: In this study, we investigated the effects of a tryptase inhibitor, APC-366, on the acute allergic airway reaction in specific pathogen-free pigs sensitized to the antigen Ascaris suum. METHODS: APC-366 (5 mg in 1 mL of water, each dose) was given as an aerosol to seven pigs two times (t); at t = - 60 min and t = - 15 min Control pigs received water. Ascaris antigen (in 2 mL saline) was nebulized to the airways over approximately 5 min at t = 0. All aerosols were generated with an ultrasonic nebulizer. RESULTS: The allergen challenge caused an acute reaction with a significant increase in airway resistance (R(aw)) in the control pigs from 3.3 +/- 0.6 cmH20/l/s to 10.2 +/- 2.3 cmH20/l/s, while in the APC-366-treated pigs, the R(aw) increased from 2.6 +/- 0.4 cmH20/l/s to 4.5 +/- 0.7 cmH20/l/s (P < 0.05 compared to controls). The dynamic lung compliance (C(dyn)) decreased significantly in the control pigs, but not in the APC-366-treated animals. The histamine concentration in urine in the control pigs was elevated immediately after allergen challenge, while this release was markedly reduced in the APC-366-treated pigs. CONCLUSION: The tryptase inhibitor APC-366 reduces the acute airway response to allergen significantly. There is also a reduced elevation in urine histamine concentration after challenge in the treated pigs, compared to controls. These results indicate that inhibition of mast cell tryptase might be a useful anti-allergic treatment in asthma.     

Induction of allergic inflammation in the lungs of sensitized sheep after local challenge with house dust mite

Background Previous sheep models of asthma are based on sheep sensitized to nematode (Ascaris) allergens and these have been used to evaluate the physiological and pharmacological effects of potential anti‐asthma agents. The immunological mechanisms associated with the allergic response in sheep lungs has not been examined in detail. Objective To develop an experimental sheep model of allergic lung inflammation based on a relevant major human allergen, house dust mite, and to define the immunological features of the allergic response in this model. Methods Sheep immunized subcutaneously with solubilized house dust mite extract were given a single bronchial challenge with house dust mite. Bronchoalveolar lavage (BAL) and peripheral blood leucocytes were collected before and after challenge for flow cytometry, and tissue samples were taken post‐mortem (48 h post‐challenge) for histology and immunohistochemical analyses. Results Immunizations with 50 μg house dust mite induced an allergen‐specific IgE response in 50 to 60% of sheep (allergic sheep), with higher antigen doses increasing specific IgG₁ but not IgE. Lung challenge of allergic sheep with house dust mite led to the initial recruitment of neutrophils (at 6 h post‐challenge) followed by eosinophils and activated lymphocytes into the lung tissue and BAL, similar to the late‐phase allergic response seen in human asthma. Eosinophil recruitment peaked at 48 h post‐challenge, representing 10 to 33% of BAL leucocytes in allergen‐challenged allergic sheep compared to 0 to 3% in allergen‐challenged control (naïve) sheep. Lymphocytes recovered from the lung after allergen challenge were enriched for CD4⁺ T cells and were more activated than lymphocytes in blood. There was significant down‐regulation of CD62L (L‐selectin) and CD49d (VLA‐4) expression after allergen challenge on BAL eosinophils and lymphocytes compared to blood. In addition, VCAM‐1 (ligand for VLA‐4) was up‐regulated on blood vessels of allergen‐challenged lungs. Eosinophils, CD4⁺ T cells and CD45R⁺ B cells were the most prominent leucocytes found in lung tissue 48 h after allergen challenge. Conclusion This study demonstrates, for the first time, the ability of house dust mite to induce allergic responses in sheep lungs. This novel sheep model of allergic lung inflammation using relevant human allergens, exhibits similarities to human asthmatic disease and will be a useful tool for studies of the immunological and physiological mechanisms of allergic asthma.     

Suppression of anaphylactic shock in sensitized guinea pigs by cytochalasin B

Twenty-three guinea pigs, presensitized with horse serum, were injected intracardially with 1 ml of 1.5 X 10(-4) M cytochalasin B in a 2.5% dimethyl sulfoxide solution, 1.5 h before being challenged with the serum. Eighteen of the guinea pigs (80%) survived. A single intracardiac injection of cytochalasin B to the control group of guinea pigs at 1.5 h before administration of the allergen did not prevent their sensitization and death following challenge.     

卡介苗对豚鼠实验性哮喘的预防性治疗作用

目的:观察卡介苗(BCG)对哮喘豚鼠的预防治疗作用。方法:采用31只豚鼠,分为3组进行处理,分别为对照组、卵蛋白(OVA)致敏组和BCG处理组。用OVA(Ⅲ级)致敏豚鼠复制豚鼠哮喘模型。结果:本模型采用10%的OVA致敏,1%的OVA激发,所有动物都表现有不同程度的过敏反应症状。实验动物在接受BCG注射后,表现为以下特点:一是外周血淋巴细胞和单核细胞增加;二是BALF中细胞分类的变化,支气管肺泡灌洗液(BALF)中以淋巴细胞的增加最为明显。 经过OVA致敏的动物BALF和肺组织中嗜酸性粒细胞(EOS)明显增加,BCG不同程度地降低肺组织EOS的气道浸润及减轻OVA致敏豚鼠的气道反应。结论:[HTSS]使用本实验体系BCG可以减轻实验性哮喘的气道炎症反应。     

氟伐他汀对哮喘气道重塑的抑制作用及机制研究

目的:探讨氟伐他汀对哮喘气道重塑过程的影响及分子机制。方法:以卵蛋白致敏的豚鼠哮喘模型为对象,观察正常对照组、哮喘组及氟伐他汀+哮喘组之间气道平滑肌肌层厚度的差异。氟伐他汀+哮喘组即每次激发哮喘前30min吸入浓度为05g/L的氟伐他汀2mL。同时采用Dot-blot分子杂交法、免疫组化SABC法检测各组气道ras基因的mRNA和蛋白水平变化。结果:哮喘组气道平滑肌层平均厚度为(7427±330)μm,显著高于正常对照组(3857±337)μm(P<001);氟伐他汀+哮喘组的平滑肌层厚度为(5170±413)μm,明显低于哮喘组(P<005)。哮喘组平滑肌细胞的ras基因表达水平明显高于正常对照组,但氟伐他汀+哮喘组未出现该基因的高表达。结论:氟伐他汀在一定程度上能抑制哮喘气道重塑的病理过程,其发挥效应的机制之一是阻断平滑肌细胞rasp21信号转导途径。