血小板在大鼠过敏性休克中的作用

用抗血小板血清耗竭致敏大鼠血小板后可明显抑制卵白蛋白诱发的过敏性休克。接受致敏大鼠血小板输注后的非致敏大鼠可在卵白蛋白攻击后产生明显的血压下降，血小板的输注量与血压下降程度呈正比，在体外，卵白蛋白可诱发致敏大鼠血小板产生化学发光，但无明显的５－羟色胺释放；反之，经典的血小板活化剂凝血酶。血小板活化因子或二磷酸腺苷在引起致敏大鼠血小板释放５－羟色胺的同时不产生明显的化学发光。电镜观察发现，在抗原攻击下只有致敏大鼠血小板能发生活化改变。这一现象有力证明血小板在速发型变态反应中的作用是通过抗原特异性机制所介导。阿魏酸钠不仅可抑制抗原诱发的过敏性休克。而且能抑制抗原诱发的血小板活化，提示其抗变态反应作用与其抑制血小板功能密切相关．     

粉尘螨滴剂对豚鼠特异性哮喘反应的脱敏作用

目的建立粉尘螨提取蛋白诱导的豚鼠哮喘模型，观察粉尘螨滴剂的脱敏作用。方法粉尘螨蛋白致敏豚鼠在抗原静脉注射攻击后测定气道阻力和肺动态顺应性；甲酰胆碱气雾吸入激发气道高反应性，计数和分类支气管肺泡灌洗液中的炎症细胞，观察肺组织病理学的改变。治疗组用粉尘螨滴剂舌下给药治疗，模型组滴入等量的生理盐水，正常对照组不作任何处理。结果模型组豚鼠经抗原攻击后气道阻力明显增加，肺动态顺应性明显降低；甲酰胆碱气雾吸入能激发气道高反应性；嗜酸性粒细胞浸润明显增加。粉尘螨滴剂治疗组与模型组比较，哮喘反应明显改善。结论粉尘螨滴剂长期舌下给药对豚鼠哮喘反应有明显的脱敏作用，为临床治疗提供了实验依据。     

血小板活化因子诱发豚鼠气道高反应性及阿魏酸钠对其的影响

正常豚鼠吸入血小板活化因子（ＰＡＦ）２４ｈ后气道对组胺引起的收缩反应性明显增高，支气管肺泡灌洗液中的嗜酸性白细胞计数明显增多。用兔抗豚鼠血小板血清选择性耗竭血小板，向气道内注入肝素，或用阿魏酸钠２５，５０和１００ｍｇ·ｋｇ－１，ｉｖ均可不同程度抑制ＰＡＦ诱发的气道高反应性和嗜酸性白细胞向肺内募集。     

小剂量哌替啶对香烟烟雾致豚鼠急性肺气道反应的影响

目的研究小剂量阿片受体激动剂哌替啶(Peth)对香烟烟雾吸入引起的豚鼠急性气道收缩反应和炎性反应的影响。方法观察Peth0.01,0.1和1mg.kg-1对豚鼠自主吸入75%香烟烟雾(含25%O2)60mL后,气道阻力和肺动态顺应性变化的影响及气道组织血管通透性变化的影响;观察Peth0.1mg.kg-1对豚鼠2h内分6次吸入(共360mL)75%浓度的香烟烟雾后,支气管肺泡灌洗液(BALF)中白细胞总数和分类计数改变的影响,测定BALF中一氧化氮(NO)含量。结果Peth能减轻或明显抑制香烟烟雾刺激后气道阻力增高和肺动态顺应性下降的反应,抑制气道组织各段微血管通透性增加的反应,降低BALF中的白细胞总数和中性粒细胞比例,降低BALF中NO的含量。结论小剂量Peth对豚鼠急性神经源性气道收缩反应和炎性反应具有抑制作用。     

α-萜品烯醇对豚鼠肺机械功能的影响

肺机械功能测定是整体动物实验中研究平喘药较好的方法。本文通过测定豚鼠的潮气量(V)、呼吸气流速度(F)和胸内压(P),描记压力—流速(P-F)曲线和压力—容量(P-V)曲线,计算肺阻力(R_L)和肺动态顺应性(Cdyn),研究艾叶油的有效平喘成分之一——α-萜品烯醇(α-Ter-pineol)对豚鼠气道的直接扩张作用,对豚鼠组胺引喘、卵白蛋白主动致敏和IgE抗血清被动致敏豚鼠实验性哮喘的保护作用,并且用心得安、利血平等工具药初步分析其作用机理,发现其作用并非通过兴奋β肾上腺素受体,亦不受肾上腺素能神经功能的影响。     

格瑞1号油和2号油对致敏豚鼠抗原攻击后肺机械功能的影响

目的：观察格瑞1号油及2号油对致敏豚鼠抗原攻击后引起肺阻力增高和动脉肺顺应性降低的影响，评估两的平喘作用。方法：采用卵白蛋白10mg和氢氧化铝凝胶200mg后腿部肌内注射致敏豚鼠，3－4周后予以抗原攻击（1％卵白蛋白）引起肺阻力（RL）和动态肺顺应性（Cdyn)变化来观察格瑞1号油和2号油药效。结果：格瑞1号油和2号油4g/kg、8g/kg均能明显抑制抗原攻击引起的RL增高，1号原油8g/kg和2号原油8g/kg能明显抑制抗原攻击引起的Cdyn降低。模型组（0.9%NaCl 4ml/kg于抗原攻击前1h,ig)在抗原攻击后RL非常明显的增高。Cdyn非常明显的降低，攻击后1－10min变化最为明显，10min后趋于逐渐恢复。1号油和2号油4g/kg、8g/kg组和沙丁胺醇4mg/kg组在抗原攻击后5、10、15min均显示出对RL增高有明显抑制作用（与模型组比较P＜0．05）。在抗原攻击后3min及20min，只有1号油8g/kg组和沙丁胺醇4mg/kg组对Cdyn降低有明显抑制作用（与模型组比较P＜0．05），而1号油4g/kg组、2号油4g/kg、2号油8g/kg组有抑制趋向，但无明显差异（P＞0．05）。在抗原攻击后5min，1号油8g/kg组和沙丁胺醇4mg/kg组对Cdyn降低均有明显抑制作用（与模型组比较P＜0．05），而其他组无明显差异（P＞0．05）。从上述结果可以观察到格瑞1号油和2号油在对致敏豚鼠抗原攻击后引起RL和Cdyn变化的高峰期内的作用比较明显，恢复的比较快。结论：格瑞1号油和2号油对致敏豚鼠抗原攻击后建立的哮喘模型呈明显保护作用。     

一种新的血小板活化因子拮抗剂E-6123

现认为支气管敏感度增高和哮喘发作均与嗜酸性细胞增加有关。人体血小板活化因子(PAF)通过多个途径影响嗜酸性细胞,例如改变细胞内钙的外流,细胞裂解或诱发产生趋药性。PAF拮抗剂能特异性地阻抑嗜酸性细胞移行。E—6123是一种具有PAF拮抗作用的噻吩并二氮(艹卓)类化合物,它在动物体内对PAF所引起的支气管收缩等具有强力的抑制作用。作者研究了本品对PAF所致肺嗜酸性细胞浸润的影响。试验动物为体重250～480g的雄性Hartley豚鼠。对抗原吸入组豚鼠先静注适量的经10倍稀释的抗卵白蛋白豚鼠血清使其被动致敏,于次日再静注2.5mg/kg美吡拉敏,5min后将豚鼠置于盒内令其吸入0.3mg/ml的卵白蛋白或生理盐水超声雾化液,每次10min。对照组给予气雾剂溶媒雾化吸     

α-萜品烯醇对豚鼠肺机械功能的影响

肺机械功能测定是整体动物实验中研究平喘药较好的方法。本文通过测定豚鼠的潮气量(V)、呼吸气流速度(F)和胸内压(P),描记压力—流速(P-F)曲线和压力—容量(P-V)曲线,计算肺阻力(R_L)和肺动态顺应性(Cdyn),研究艾叶油的有效平喘成分之一——α-萜品烯醇(α-Ter-pineol)对豚鼠气道的直接扩张作用,对豚鼠组胺引喘、卵白蛋白主动致敏和IgE抗血清被动致敏豚鼠实验性哮喘的保护作用,并且用心得安、利血平等工具药初步分析其作用机理,发现其作用并非通过兴奋β肾上腺素受体,亦不受肾上腺素能神经功能的影响。     

消咳喘片对豚鼠支气管平滑肌的影响

目的:研究消咳喘片(Xiaokechuan Tablets)对正常及致敏豚鼠支气管收缩的影响及平喘作用。方法:通过离体和整体实验,观察消咳喘片对以组胺和乙酰胆碱引起的正常豚鼠支气管的收缩和以卵蛋白诱发的致敏豚鼠支气管收缩的影响。结果:离体实验,消咳喘片52mg·L-1对组胺致正常豚鼠气管片的收缩具有对抗作用,对卵白蛋白所致的致敏豚鼠支气管平滑肌收缩有极显著的抑制作用(P<0．01)。对乙酰胆碱所致气管片收缩作用明显;整体实验,消咳喘片18mg·kg-1可显著延长卵白蛋白所致的致敏豚鼠呼吸困难,抽搐和跌倒的潜伏期(P<0．01)。结论:消咳喘片能拮抗组胺刺激引起的正常豚鼠和卵白蛋白引起的致敏豚鼠离体气管片的收缩,抑制致敏豚鼠哮喘的发生。     

吡布特罗胶囊对豚鼠支气管平滑肌的影响

目的:研究吡布特罗胶囊(PirbuteroI Capsules)对正常及致敏豚鼠支气管收缩的影响及平喘作用。方法:通过离体和整体实验,观察 Pributerol Capsules 对以组胺和乙酰胆碱引起正常豚鼠支气管的收缩和以卵白蛋白诱发的致敏豚鼠支气管收缩的影响。结果:离体实验,PirbuterolCapsules 52mg·L~(-1)对组胺致正常豚鼠气管片的收缩具有对抗作用,对卵白蛋白所致的致敏豚鼠支气管平滑肌收缩有极显著的抑制作用(P<0.01)。对乙酰胆碱所致气管片收缩作用明显;整体实验,Pirbuterol Capsules 18mg·kg~(-1)可显著延长卵白蛋白所致的致敏豚鼠呼吸困难,抽搐和跌倒的潜伏期(P<0.01)。结论:Pirbuterol Capsules 能拮抗组胺刺激引起的正常豚鼠和卵白蛋白引起的致敏豚鼠离体气管片的收缩,抑制致敏豚鼠哮喘的发生。     

Inhibitory effects of cryptoporus polysaccharide on airway constriction, eosinophil release, and chemotaxis in guinea pigs

AIM: To study effects of cryptoporus polysaccharide (CP) on antigen-induced bronchoconstriction, eosinophil peroxidase (EPO) release in vivo, and on platelet activating factor (PAF)-induced eosinophil chemotaxis in vitro in guinea pig. METHODS: The asthma model of guinea pig was formed with ovalbumin (OVA). The changes of lung resistance (RL) and dynamic lung compliance (Cdyn), EPO level in bronchoalveolar lavage fluids (BALF) and eosino- phil migration were determined. RESUL…     

Antigen-induced hyperresponsiveness to methacholine in ventilated, anesthetized guinea pigs.

Guinea pigs were actively sensitized to ovalbumin and exposed 2-3 weeks later to an aerosol of ovalbumin or saline. Changes in lung function were assessed 0.5, 1, 6, 24 and 72 h later by measuring the peak increase in pulmonary inflation pressure induced by i.v. methacholine during constant-volume ventilation. Responses to methacholine were significantly potentiated at 0.5, 1, 6 and 24 h but not at 72 h following exposure to antigen. Hyperresponsiveness to methacholine was maximal at 0.5-1 h and, in terms of magnitude, comparable to the early increase in airway reactivity found in mild asthmatics after allergen challenge. Whether the hyperresponsiveness to methacholine induced by antigen in the guinea pig can be attributed solely to an increase in airway reactivity or is due, at least in part, to decreased lung compliance requires further study.     

The effect of prophylactic anti-asthma drugs on PAF-induced platelet accumulation in the thorax of the guinea pig

Intravenous infusion of platelet activating factor (PAF) causes an accumulation of platelets within the thorax of the guinea pig that is accompanied by increased sensitivity of the airways to spasmogens. A crystal scintillation detector has been used for measurement of intrathoracic accumulation of 111Indium-labeled platelets during responses to PAF. PAF-antagonists inhibit development of airway hyperreactivity, do not diminish platelet accumulation in response to an intravenous infusion of PAF. It is therefore concluded that intrathoracic platelet accumulation per se is not the determinant of increased airway reactivity.     

Biochemical and pharmacological characterization of ICI 198,615: a peptide leukotriene receptor antagonist

ICI 198,615 is one representative of a new chemical class of peptide leukotriene receptor antagonists that are the most potent and selective described to date. ICI 198,615 antagonized LTC4-, LTD4- and LTE4-induced increases in cutaneous vascular permeability in the guinea pig, with i.v. ED50 values of 0.083, 0.11 and 0.067 mumol/kg, respectively. Against LTD4, ICI 198,615 was 615 and 415 times more potent than LY 171883 and FPL 55712, respectively. L-Serine borate, an inhibitor of the metabolism of LTC4 to LTD4, did not influence the antagonism by ICI 198,615 of LTC4-induced increases in cutaneous vascular permeability. The compound both inhibited and reversed aerosol ovalbumin antigen-induced increases in pulmonary resistance in passively sensitized guinea pigs, but demonstrated little ability to inhibit or reverse ovalbumin antigen-induced decreases in dynamic lung compliance. At concentrations ranging from 10(-8) to 10(-5) M, ICI 198,615 had no significant effect on either the spontaneous or ovalbumin antigen-induced release of histamine, peptide leukotrienes, thromboxane B2 or 6-keto-prostaglandin F1 alpha from chopped guinea pig lung. At 10 microM, the compound did not inhibit 5-, 12- or 15-lipoxygenase. Finally, ICI 198,615 antagonized LTD4-induced increases in TxB2 release from chopped guinea-pig lung.     

班布特罗对豚鼠支气管收缩反应的扩张作用

观察班布特罗对豚鼠支气管收缩反应的影响。方法：用哮喘发作潜伏期,肺机械功能及离体气管平滑肌松弛试验观察班布特罗的支气管扩张作用。结果：班布特罗ｉｇ后１ｈ,４ｈ和２４ｈ均能延长组胺诱导的豚鼠哮喘潜伏期,ＥＤ５０分别为０．７４,０．７５,１．００ｍｇ．ｋｇ＾－１,其作用持续时间明显长于特布他林。     

The effect of prophylactic anti-asthma drugs on PAF-induced airway hyperreactivity

Intravenous injection of platelet activating factor (PAF) in anesthetized guinea pigs induces non-selective airway hyperreactivity. This response to PAF was reduced in a dose-dependent manner by systemic administration of established prophylactic anti-asthma drugs (ketotifen, cromoglycate, aminophylline and glucocorticosteroids) and by competitive antagonists of PAF. These inhibitory effects could not be accounted for by antagonism of histamine (H1), serotonin or peptidoleukotrienes receptors; parasympatholytic activity; cyclo-oxygenase or lipoxygenase inhibition; mast cell stabilization; or bronchodilatation. Infusion or injection of PAF to induce airway hyperreactivity in the guinea pig may provide a prospective test for prophylactic anti-asthma drugs.     

Hydrogen Peroxide-Induced Broncho- and Vasoconstriction in the Isolated Perfused and Ventilated Guinea Pig Lung

Abstract: The effect of hydrogen peroxide on perfusion flow, airway conductance (G_aw) and dynamic compliance (C_dyn) of isolated perfused and ventilated guinea pig lungs was investigated. Hydrogen peroxide (50 μM in the perfusion buffer) induced a decrease in G_aw and C_dyn and perfusion flow during 5 min. of exposure. Hydrogen peroxide also caused an increase in the levels of thromboxane in the perfusate of the lung. The constrictor effects as well as the formation of thromboxane were inhibited by the cyclooxygenase inhibitor ibuprofen (50 μM). The thromboxane/prostaglandin endoperoxide receptor antagonist L-670,596 (1 μM) abolished the effects of hydrogen peroxide on perfusion flow, G_aw and C_dyn, but did not affect the formation of thromboxane. The thromboxane-synthetase inhibitor carboxyheptylimidazole (100 μM) reduced both the hydrogen peroxide-induced formation of thromboxane and vaso- and bronchoconstriction, suggesting a predominant role for thromboxane A₂ versus prostaglandin H₂ in these effects. A role for platelet-activating factor in mediating the effect of hydrogen peroxide could not be supported, as the platelet-activating factor receptor antagonist WEB 2086 (10 μM) did not affect hydrogen peroxide induced vaso- and bronchoconstriction. The results of this study show that hydrogen peroxide induces thromboxane A₂ mediated vaso- and bronchoconstriction in the isolated perfused and ventilated guinea pig lung. Platelet-activating factor does not appear to play a significant role in the hydrogen peroxide-induced vaso- and bronchoconstriction. Our results also suggest that the perfused guinea pig lung is more sensitive to hydrogen peroxide than the perfused rat lung.     

ACE-inhibitor-induced enhancement of spontaneous and IgE-mediated histamine release from mast cells and basophilic leukocytes and the modulatory effect of capsaicin sensitive nerves

Frequently reported adverse inflammatory skin and airway reactions have been reported in subjects being medicated with angiotensin converting enzyme (ACE)-inhibitors. Intradermally evoked wheal and flare reactions to ovalbumin, capsaicin and bradykinin, in ovalbumin sensitized guinea pigs, was previously demonstrated to be enhanced by pretreatment with the ACE-inhibitor MK 422 (the active parent diacid of enalapril). In vitro results from this study demonstrate that the ACE-inhibitor MK 422 degranulated guinea pig lung and skin mast cells as well as human basophils, and enhanced allergen-evoked histamine release. Local capsaicin pretreatment in vivo of guinea pig skin decreased spontaneous and allergen-triggered release of histamine in vitro from skin mast cells. No clear enhancing effect of MK 422 was seen on the allergen-triggered histamine release in vitro from capsaicin pretreated skin, and the spontaneous release was unaffected by the ACE-inhibitor. The allergen-triggered wheal and flare reaction in ovalbumin sensitized guinea pigs was potentiated by MK 422 and the late phase reaction of the inflammatory response was especially augmented. Capsaicin pretreatment of the guinea pigs abolished this late phase reaction as well as the inflammatory enhancing effect of MK 422. Our in vitro results from capsaicin pretreated skin indicate that the reduced inflammatory response in vivo in capsaicin pretreated skin is due not only to capsaicin induced depletion of neuropeptides from sensory nerves, but also to secondary degranulation of mast cells by one or more of these peptides.     

Effect of NZ-107 on late-phase airway responses and airway hyperreactivity in guinea pigs

The effect of NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) on late-phase airway responses and airway hyperreactivity was investigated in the guinea pig. Challenge with inhaled ovalbumin in conscious guinea pigs actively sensitized with inhaled ovalbumin caused triphasic bronchial obstruction, which peaked at 5-30 min, 6-8 h and 24 h. In this model, airway hyperreactivity to acetylcholine was observed 48 h after antigen challenge. Orally administered NZ-107, given 2 h before ovalbumin challenge significantly inhibited airway responses at 5-30 min (10 mg/kg), 6-8 h (30 mg/kg), 24 h (10 mg/kg) and airway hyperreactivity (30 mg/kg). When NZ-107 (10 mg/kg) was orally administered to the guinea pigs 3 h after ovalbumin challenge, it also inhibited airway responses at 6-8 h and 24 h and airway hyperreactivity. In anaesthetized guinea pigs, intravenous administration of NZ-107 (0.03-1.0 mg/kg) inhibited platelet-activating factor (PAF)- and propranolol-induced airway hyperreactivity to histamine. These results suggest that NZ-107 may be a useful drug for the treatment of bronchial asthma by reducing late-phase airway responses and airway hyperreactivity.