内毒素在支气管高反应性形成中的作用

内毒素在支气管高反应性形成中的作用陈剑雄，吴红霞，万有，曹永舒（药理教研室）观察了以内毒素作为致病原在支气管高反应性形成中的作用。结果：豚鼠腹腔注射内毒素后，其气道对组织胺引起哮喘潜伏期明显缩短，组织胺收缩离体气管平滑肌的ＰＤ２值明显增高。异丙肾上腺...     

内毒素对呼吸道上皮分泌内皮素、血栓烷素、前列腺素E_2的影响及氧自由基的介导作用

目的探讨内毒素对培养小牛呼吸道上皮分泌内皮素－１（ＥＴ－１）、血栓烷素（ＴＸＡ２）、前列腺素Ｅ２（ＰＧＥ２）的影响，并探讨氧自由基的介导作用。方法大肠杆菌内毒素（ＬＰＳ）与培养小牛呼吸道上皮细胞孵育４小时后，测定培养呼吸道上皮细胞上清液中ＥＴ－１、ＴＸＡ２、ＰＧＥ２的含量。结果内毒素可明显促进小牛呼吸道上皮细胞ＥＴ－１、ＴＸＡ２的分泌，抑制ＰＧＥ２分泌，并呈浓度依赖性，用氧自由基清除剂ＳＯＤ、Ｃａｔ预处理呼吸道上皮细胞可拮抗内毒素的作用。结论内毒素诱发支气管高反应性形成，可能与其促进呼吸道上皮分泌ＥＴ－１、ＴＸＡ２，抑制ＰＧＥ２分泌有关，氧自由基可能参与其诱发支气管高反应性过程。     

甘草酸单铵对内毒素诱发支气管高反应性的作用－β－cAMP向下调节影响

甘草酸单铵对内毒素诱发支气管高反应性的作用－β－ｃＡＭＰ向下调节影响陈剑雄（衡阳医学院药理教研室）曹永舒（河南医科大学药理教研室）内毒素１ｍｇ／ｋｇｉｐｄ４豚鼠气道Ｈｉｓ引喘潜伏期明显缩短，Ｈｉｓ反应性增强，其ＰＤ２值增大，β受体功能降低，ＩＳＯ的Ｐ...     

心脉灵液对内毒素休克大鼠血浆和肺溶酶体酶含量的影响

在内毒素休克大白鼠模型上观察到肺系数明显增高，支气管肺泡灌洗液（ＢＡＬ）中的分子量４０Ｓ萤不素右旋酿酥（ＦＤ—４０Ｓ）含量明显上升，同时血浆及肺组织酸性磷酸酶（ＡＣＰ）增高，与正常对照组相比有明显差异（Ｐ＜０．０１）；用心脉灵液进行治疗，肺系数及ＢＡＬ中ＦＤ—４０Ｓ含量均下降，血浆及肺组织ＡＣＰ也降低，因此说明内毒素引起的肺血管通透性增加与溶酶体酶的释放有密切的关系，而心脉灵液可通过抑制溶酶体的释放而减轻溶酶体酶对肺组织的损伤，从而起到保护肺组织的作用。     

氧自由基对豚鼠呼吸道的作用及其机制的初步探讨

在豚鼠离体支气管肺灌流系统及兔胸主动脉淋浴灌流系统中10mA电解克氏液2min,支气管肺灌注压显著增高(p<0.01),组织胺反应性明显增强(p<0.01),兔胸主动脉乙酰胆碱诱导内皮细胞释放的内皮衍生松弛因子明显减少(p<0.01),而羟自由基清除剂显著性抑制电解性氧自由基的作用。结果提示氧自由基可诱发离体肺收缩及支气管高反应性产生。     

内皮素及前列环素在内毒素血症所致肝损害中的作用

目的：探讨内皮素－１（ＥＴ－１）及前列腺环素（ＰＧＩ２）在内毒素在血症所致肝损害中的作用。方法：选用Ｗｉｓｔａｒ大鼠１２０只，分为对照组，内毒素组，内毒素＋ＥＴ－１抗体组，内毒素＋前列环素组。观察了伤后３、６、９、１２和２４ｈ血浆中ＥＴ－１谷丙转氨酶（ＧＰＴ）的含量，肝组织中ＥＴ－１，ＰＧＩ２，乳酸脱氢酶（ＬＤＨ）和丙二醛（ＭＤＡ）的含量，结果：内毒素血症时，血浆和肝组织中ＥＴ－１明显升高，血浆Ｇ     

大黄对实验性急性化脓性胆管炎早期血浆内毒素含量的影响

取ＳＤ大鼠，随机分为三组：正常组、盐水组、大黄组。利用大肠杆菌诱发急性化脓性胆管炎，盐水组和大黄组分别经口灌服生理盐水和大黄１ｍｌ／１００ｇ·日。以血浆内毒素及血清酶学为指标，观察了大黄对大鼠急性化脓性胆管炎早期血浆内毒素及肝功的影响。结果显示：１．盐水组术后３天内死亡４只，大黄组死亡２只，正常组无死亡。２．盐水组大鼠术后３天血浆内毒素含量明显升高，大黄组含量较盐水组明显降低（Ｐ＜０．０１）。３．术后３天血清ＡＫＰ和ＧＰＴ与正常组比均有明显增高，而盐水和大黄组之间无显著性差异（Ｐ＞０．０５）。结果表明大黄具有降低化脓性胆管炎大鼠的早期死亡率及显著降低内毒素血症的作用。     

地塞米松对大鼠内毒素肝损伤保护作用的探讨

Ｗｉｓｔａｒ大白鼠腹腔注射Ｅ．ｃｏｌｉ内毒素纯制剂（２ｍｇ／Ｋｇ体重），１２小时后，其肝脏线粒体琥珀酸脱氢酶（ＳＤＨ）活力显著降低（Ｐ＜０．０１），胞浆还原型谷胱甘肽（ＧＳＨ）水平明显下降（Ｐ＜０．０５）。线粒体内丙二醛类脂质过氧化物（ＬＰＯ）含量和超氧化物歧化酶（ＳＯＤ）活力显著增加（Ｐ均小于０．０１）。线粒体膜脂质成分ＰＥ、ＰＳ、ＰＣ含量均明显下降，ｌｙＳｏ－ＰＣ显著增加。组织学和电镜观察表现为一定程度的肝细胞损伤。用地塞米松按４ｍｇ／Ｋｇ体重，分别在内毒素处理的同时、２小时后４小时后注射。结果显示：同时注射和２小时后注射组，上述各项生化指标与内毒素组比较均有显著改善，而４小时后注射组无明显改善。     

组织蛋白酶D、P糖蛋白及Her-2与贲门癌预后关系的研究

探讨组织蛋白酶Ｄ（Ｃａｔｈ－Ｄ）、Ｐ糖蛋白（Ｐ－ｇｐ）及Ｈｅｒ－２与贲门癌治疗预后的关系。方法应用免疫组织化学的方法，检测了４３例贲门癌经手术切除的新鲜癌组织标本中的Ｐ糖蛋白、组织蛋白酶Ｄ及Ｈｅｒ－２的表达水平，并结合其病理类型及淋巴结转移进行了综合判定。结果Ｐ糖蛋白及Ｈｅｒ－２的表达与贲门癌的淋巴结转移无统计学意义，（Ｐ＞０．０５），而组织蛋白酶Ｄ的表达与贲门癌的淋巴结转移有显著相关（Ｐ＜０．０１），同时组织蛋白酶Ｄ阳性者其Ｐ糖蛋白及Ｈｅｒ－２的表达也明显高于组织蛋白酶Ｄ阴性者。贲门癌的分化程度与Ｐ糖蛋白及组织蛋白酶Ｄ的表达无显著差异，而与Ｈｅｒ－２的表达却有显著相关（Ｐ＜０．０５）。结论组织蛋白酶Ｄ阳性的贲门癌易发生淋巴结转移，Ｈｅｒ－２阳性者恶性度高且预后差，临床上对上述病人应给予特殊针对性的治疗方案。     

虎杖甙对大鼠血管平滑肌细胞膜电位的影响

利用荧光染料和粘附式细胞仪观察虎杖甙（ＰＤ）对大鼠ＶＳＭＣ膜电位的影响。结果显示，给ＰＤ（０．４ｍｍｏｌ／Ｌ）５ｍｉｎ后，ＶＳＭＣ膜电位出现去极化。α肾上腺素能受体拮抗剂利及丁、组织胺受体拮抗剂甲氰咪胍和钙通道阻断剂维拉帕米分别预处理并不能阻断ＰＤ的去极化作用；但加入钠通道阻断剂河豚毒素（２μｍｏｌ／Ｌ）和钾通道阻断剂优降糖（２．５μｍｏｌ／Ｌ）都能显著抑制ＰＤ的去极化作用。提示ＰＤ使正常细胞膜去极化作用可能与钠、钾通道开放有关，并可能受α肾上腺素能受体、组织胺受体及钙通道的调节     

变应性鼻炎与气道高反应性的相关性

[目的]观察变应性鼻炎早期反应与气道高反应性的关系,明确临床病理因子．[方法]随机选择变应性鼻炎患者73例及无变应性鼻炎的健康者36例作为研究对象．随机选择29例变应性鼻炎患者应用组按做鼻黏膜诱发刺激试验,30min后观察气道高反应性、肺功能及肺过敏性的变亿;对剩余44例变应性鼻炎患者及36例非变应性鼻炎者行气道黏膜诱发试验,以乙酰甲胆碱作为气道黏膜刺激物,刺激后气道与肺部的症状用视觉模拟评分法记录,并调查鼻腔容积的变化与鼻部症状．[结果]变应性鼻炎患者气道高反应性发生率较非变应性鼻炎患者显著增高．变应性鼻炎分型中（ARIS分类法）持续一中度、重度型是气道高反应性增加有价值的因素．[结论]变应性鼻炎早期反应与气道高反应性之间具有显著相关性,变应性鼻炎的持续．中度、重度型患者气道高反应性的增多可能是较重要的发病因素之一．     

A comparison of regular with intermittent bronchodilators in asthma patients on inhaled steroids

The aim of this study was to compare the effect of regular versus intermittent (p.r.n.) bronchodilators on bronchial reactivity and asthma control in patients on concomitant inhaled corticosteroids. We studied 12 patients with asthma in a prospective, randomised, single-blind, single-dummy, three-period crossover trial comparing placebo (2 puffs t.d.s.), salbutamol (200μg t.d.s.) and oxitropium bromide (200μg t.d.s.) for 28 days each. Computerised spirometry and bronchial reactivity to histamine were obtained on entry and after each treatment period. Symptom scores, use of rescue bronchodilator and peak expiratory flow rates were recorded daily. There were no significant differences in bronchial hyperreactivity between the salbutamol, oxitropium and placebo treatment periods. There were no significant differences in baseline FEV₁, FEF_25–75%, symptom scores, use of rescue bronchodilator or morning and evening PEFR between treatment periods. Intermittent beta agonist therapy is as effective as regular therapy in terms of asthma control and bronchial hyperreactivity in patients on concomitant inhaled corticosteroid therapy. Since intermittent therapy achieves similar results with significantly lower beta agonist consumption, the data support current recommendations that beta agonists should be taken on a p.r.n. basis in asthma patients on inhaled steroids.     

过氧亚硝基阴离子致豚鼠气道反应性增高的实验研究

目的 探讨过氧亚硝基阴离子（ＯＮＰＰ－）在气道上皮损伤致气道高反应性中的作用。方法 以离体豚鼠气管条建立组织胺累积－浓度反应曲线，电镜观察气道上皮细胞的形态学变化。结果 豚鼠气管条与ＯＮＯＯ－孵育后，气管条的反应性增高，同时电镜观察有气道上皮细胞损伤脱落。结论 ＯＮＯＯ－参与了气道上皮细胞的损伤，并导致了气道高反应笥的形成。     

The effect of fresh orange juice on bronchial hyperreactivity in asthmatic subjects

We studied 16 mild stable asthmatic subjects to determine if orange juice increases nonspecific bronchial hyperreactivity (NSBH). In 9 subjects, bronchial responsiveness to histamine was assessed before and after water ingestion on the control day, and orange ingestion on a consecutive day. The mean (+/- SD) ratio of log10 PD20 FEV1 after water: log10 PD20 FEV1 before water (1.00 +/- 0.13) was not significantly different from the mean (+/- SD) ratio of log10 PD20 FEV1 after orange: log10 PD20 FEV1 before orange (0.97 +/- 0.12). To avoid the possibility of histamine tachyphylaxis, 7 subjects participated in a second protocol in which histamine PD20 FEV1 was determined on a control day (geometric mean 0.11 mg.) and again two days later, thirty minutes after ingestion of orange juice (geometric mean 0.06 mg). There was no significant difference in the PD20 FEV1 (p = 0.344). Our data show that ingestion of fresh orange juice per se did not heighten NSBH in our subjects. (PD20 FEV1 is the dose of histamine required to produce a twenty percent fall in forced expiratory volume in one second [FEV1]).     

The pathophysiology of asthma

Because postmortem studies of humans provide little information on the initial pathophysiologic events in asthma, animal models have been developed. Recently the Ascaris-allergic rhesus monkey has provided an opportunity to examine the onset of pathophysiologic changes following challenge and to correlate them with airway structure. These studies have suggested that the initial interaction between antigen and mast cells may occur in the bronchial lumen or in the epithelium superficial to the tight junctions, where a small but significant percentage of airway mast cells exist. It also appears that this initial antigen-antibody interaction results in the release of mediators that both stimulate the rapidly adapting stretch receptors in the mucosa and alter the mucosal barrier so that proteins of large molecular weight can penetrate. The fact that antigen challenge results in hyperresponsiveness to a subsequent dose of inhaled histamine and increased systemic absorption of histamine suggests that the airway hyperresponsiveness could be related to increased penetration of histamine into the bronchial wall. These observations suggest that the initial event in an acute asthmatic attack is the release of mediators from superficial mast cells, and that this amplifies the allergic response by altering the mucosal permeability so that more antigen reaches the submucosal mast cells. This altered permeability may also help explain the hyperreactivity of the airways to nonspecific airway stimulants in persons with asthma.     

顽固性咳嗽的误诊分析

目的：准确诊断咳嗽变异性哮喘。方法：随机抽取66例病因不明的咳嗽患者。选用美国森迪斯公司生产的Vmax6200型体积描记仪,以乙酰甲胆碱为气道激发剂,进行气道激发试验检测,观察其气道反应性。结果：45.6%的患者符合诊断变异性哮喘。结论：气道激发试验对非典型哮喘诊断有着重要的临床价值。     

Lack of Correlation between the Grade of Methacholine-Induced Bronchial Hyperreactivity and Ipratropium Bronchodilation in Asthmatics

Abstract

In 46 never-smoking randomly chosen patients with non-allergic asthma, 40 to 60 years old, a methacholine hyperreactivity test and lung function tests were performed after inhalation of different doses of ipratropium bromide (IB). The grade of hyperreactivity was measured as the cumulative dose of methacholine necessary to produce a decrease in the forced expiratory volume in one second of 20% of the lowest post-NaCl value (PD20). The following lung function tests were carried out: Lung volumes, ventilatory capacity including flow-volume curves, airway resistance and nitrogen single-breath wash-out test. The bronchodilator effect, measured as a change in the different lung function tests for different doses of IB given (0.08 mg, 0.15 mg and 0.25 mg), was correlated to the grade of hyperreactivity (PD20 dose). No or only a slight correlation was found between the grade of methacholine-induced hyperreactivity and the bronchodilator effects of the different doses of IB. These results indicate a lack of correlation between an anticholinergic bronchodilator effect and the grade of methacholine-induced bronchial hyperreactivity, or possibly an insensitivity of the above-mentioned methacholine test.     

Bronchial hyperreactivity to leucotriene D4 and histamine in exogenous asthma

Reactivity of the small and large airways to inhaled leucotriene D4, one of the leucotrienes that constitute slow reacting substance of anaphylaxis, was studied in eight patients with exogenous asthma and nine healthy subjects with no history of atopy. Non-cumulative dose response relations were constructed for leucotriene D4 in a randomised, double blind set up. Reactivity to the leucotriene was compared with reactivity to histamine in the two groups. Both groups reacted to leucotriene D4 with significant airway obstruction evident in forced expiratory volume in one second (FEV1), peak expiratory flow rate, maximal expiratory flow rate at 30% of forced vital capacity estimated from a partial flow volume curve initiated at 50% of vital capacity (V30), and an increase in volume of trapped gas. The airways of the patients were significantly (p less than 0.01) more reactive to leucotriene D4 than those of the controls. The differences were in order of magnitude, 10(2)-10(3) for FEV1 but only about 15 for V30 (p less than 0.05). The hyperreactivity of the airways of the asthmatic subjects to leucotriene D4 was comparable to that to histamine. Inhalation of leucotriene D4 caused pronounced dyspnoea only among the patients. The findings suggest a role for leucotriene D4 in human bronchial asthma.     

Occupational asthma due to ozone

Ozone increases bronchial reactivity in normal and atopic subjects. Ozone is produced by high voltage electric discharge. Persons with pre-existent bronchial hyperreactivity should be excluded from work where significant exposure to ozone can occur. We describe a case of occupational asthma due to ozone. The levels of ozone were about 0.04 ppm.