吸入性糖皮质激素对咳嗽变异性哮喘的气道炎症和高反应性的影响

目的探究与分析吸入性糖皮质激素对咳嗽变异性哮喘的气道炎症和高反应性的影响。方法选取我院收治的咳嗽变异性哮喘患者30例和通气功能正常、体检健康者30例作为研究对象,分为病例组和对照组。病例组患者给予规范、系统的糖皮质激素吸入治疗1年,观察和对比病例组患者治疗前后以及对照组支气管舒张实验、支气管激发功能检查以及痰诱导实验检查结果。结果治疗前,病例组嗜酸性粒细胞占其他炎症细胞的(7.16±3.23)%,明显高于对照组的(3.07±1.82)%,差异有统计学意义(P0.05);治疗前,两组第1秒用力呼吸容积(FEV1)、第1秒用力呼吸容积占用力肺活量的比例(FEV1/FVC)相比,差异无统计学意义(P0.05);病例组治疗前后比较,提示气道反应性的FEV1-PD20逐渐升高,与治疗前相比,差异有统计学意义(P0.05),气道炎症水平的IL-5逐渐降低、IL-10逐渐升高,与治疗前相比,差异有统计学意义(P0.05)。结论咳嗽变异性哮喘患者经过糖皮质激素长期、规范化治疗,气道炎症得到有效控制、气道高反应性明显好转,值得推广。     

罗红霉素对哮喘大鼠气道炎症及气道高反应性的影响

目的 观察罗红霉素对哮喘大鼠气道炎症、气道高反应性的影响。方法 30只雄性SD大鼠随机分组和建模,罗红霉素干预28天,检测气道反应性和支气管肺泡灌洗液中的IL-4、IL-5、IFN-γ。结果 罗红霉素组气道反应性以及BALF中IL-4、IL-5低于哮喘组。有显著性差异;结论 罗红霉素具有减轻哮喘大鼠气道炎症和气道反应性。     

疏风宣肺法对咳嗽变异性哮喘患者气道高反应的影响

目的：探讨疏风宣肺法对咳嗽变异性哮喘患者气道高反应的影响。方法：对120例咳嗽变异性哮喘患者，随机分为中药治疗组60例和西药对照组舒氟美加必可酮气雾剂60例。观察治疗前后症状、气道反应性的变化情况。结果：治疗组控显率、总有效率分别为71．67％和88．33％；对照纽控显率、总有效率分别为41．67％和66．67％。结论：疏风宣肺法具有抗气道变应性炎症(AAI)，降低气道高反应性(BHR)的作用。     

香青兰总黄酮对哮喘大鼠气道炎症及高反应性的改善作用

目的 研究香青兰总黄酮对哮喘大鼠气道炎症及高反应性的影响。方法 采用氨水引咳实验和磷酸组胺-氯化乙酰胆碱引喘实验观察香青兰总黄酮的镇咳、平喘作用;同时观察香青兰总黄酮对哮喘大鼠支气管肺泡灌洗液(BALF)中白细胞分类计数和离体气管螺旋条张力的影响。结果 香青兰总黄酮中、高剂量能延长小鼠咳嗽潜伏期,减少小鼠2 min内咳嗽次数(P<0.05或P<0.01),延长豚鼠引喘潜伏期(P<0.01);降低哮喘大鼠血清卵白蛋白特异性IgE水平(P<0.01),减少BALF中嗜酸性粒细胞数量(P<0.01)及减小离体气管螺旋条张力(P<0.05或P<0.01)。结论 香青兰总黄酮具有一定镇咳、平喘作用;可改善哮喘气道炎症及高反应性。     

强的松对哮喘小鼠气道T淋巴细胞炎症的影响

目的：研究强的松对小鼠气道T淋巴细胞炎症的影响。方法：卵蛋白致敏及激发制成小鼠哮喘模型。免疫组化方法测定强的松对气道T淋巴细胞亚群的影响。结果：哮喘小鼠气道组织CD25^ 、CD4^ 、CD8^ 细胞的数目较正常对照组明显增多；哮喘小鼠应用强的松后气道组织CD25^ 、CD4^ 、CD8^ 细胞的数目较哮喘组明显减少。结论：1、哮喘小鼠气道组织存在T淋巴细胞的活化加强及浸润。2、小剂量强的松能抑制哮喘小鼠气道T淋巴细胞活化及浸润。     

舒利迭雾化吸入对哮喘小鼠气道炎症及气道重构的影响

目的 研究舒利迭雾化吸入对哮喘小鼠炎症及气道重构的影响.方法 将30只雄性小鼠随机分成卵白蛋自(OVA)致敏致哮喘组(A组)、舒利迭干预组(B组)、正常对照组(C组).用OVA进行致敏和激发,建立哮喘模型.收集小鼠支气管肺泡灌洗液(BALF)行白细胞和嗜酸粒细胞(EOS)计数,采用医学图像分析软件测定支气管各项指标;HE染色观察组织形态学变化.结果 正常对照组、哮喘组、舒利迭干预组的EOS分别是(0.54±0.16)、(6.82±0.5 7)、(3.19±0.66)×10<'5>/m1,A组气道壁炎性细胞计数、气道平滑肌面积、气道内壁面积均明显高于C组,两组比较差异有统计学意义(P<0.01),B组各项指标均明显低于A组,差异有统计学意义(P<0.01),B组与C组比较各项均有升高,差异有统计学意义(P<0.01,P<0.05).结论 舒利迭雾化吸入不仅可明显抑制哮喘小鼠的气道炎症反应,还可明显减轻气道重构的程度.     

阳离子气道吸入线性调控疗法可减少过敏性哮喘病人的气道炎症

2012年5月21日,Pulmatrix生物技术公司公布了其研发的治疗呼吸系统疾病的新疗法——阳离子气道吸入线性调控疗法（iCALMTM）的临床研究结果。     

气道反应测定诊断不典型哮喘

利用组织胺激发试验测定以咳嗽胸闷为主要表现病人的气道反应性２５例，其中阳性４例（１６％）、可疑阳性７例（２８％）、阴性１４例（５６％）。结果表明：（１）组织胺支气管激发剂试验是诊断不曲形哮喘的有效手段；（２）哮喘可表现为不同形式，哮鸣音不是诊断哮的唯一条件，而气道反应性增高是诊断哮提必备条件。     

1,8-桉油精对卵白蛋白致哮喘豚鼠的气道高反应性和炎症的抑制作用

目的探讨1,8-桉油精(1,8-cineol)对哮喘豚鼠肺功能的改善作用及其机制。方法豚鼠第0天和第7天ip给予0.5ml含卵白蛋白(OVA)20μg的氢氧化铝凝胶致敏,28d后OVA攻击制备哮喘模型。观察豚鼠OVA攻击后1h,1,8-桉油精10,30和100mg.kg-1对豚鼠吸入OVA后1,2,3,4,10,20和30min时气道阻力(Raw)和肺顺应性(Cdyn)变化及支气管肺泡灌洗液(BALF)中白细胞数和细胞分类的影响,并测量豚鼠肺组织中嗜酸细胞阳离子蛋白(ECP)、白细胞介素4(IL-4)、IL-8和肿瘤坏死因子α(TNF-α)的含量。观察豚鼠OVA攻击后17h再吸入乙酰甲胆碱(MCh)后,1,8-桉油精10,30和100mg.kg-1对Raw和Cdyn及BALF中白细胞数和细胞分类的影响,并测量豚鼠肺组织中ECP,IL-4,IL-8和TNF-α的含量。结果与正常对照组比较,豚鼠OVA攻击后1h,在4min时模型组Raw达到高峰;与模型组比较,1,8-桉油精30和100mg.kg-1明显抑制Raw增加(P<0.05);在3min时模型组Cdyn达到高峰,与模型组比较,1,8-桉油精10,30和100mg.kg-1均能明显抑制Cdyn降低(P<0.05);模型组豚鼠肺组织ECP,IL-4和TNF-α含量明显高于正常对照组(P<0.05);1,8-桉油精100mg.kg-1组ECP,IL-4和TNF-α含量均明显低于模型组(P<0.05),模型组与正常对照组豚鼠肺组织IL-8含量无明显差异。与模型组比较,1,8-桉油精100mg.kg-1能明显减少BALF中白细胞数和嗜酸性粒细胞比例(P<0.05)。致敏豚鼠OVA攻击17h后,模型组豚鼠Raw与正常对照组比较显著升高(P<0.05),模型组豚鼠Cdyn与正常对照组比较有显著性差异(P<0.01),1,8-桉油精100mg.kg-1对MCh引起的Raw的增加有明显的抑制作用,1,8-桉油精10,30和100mg.kg-1对MCh引起的Cdyn降低有明显的改善作用;与模型组相比,1,8-桉油精100mg.kg-1能明显减少BALF中白细胞数和中性粒细胞比例,降低肺组织ECP,IL-8和TNF-α含量(P<0.01);模型组与正常对照组豚鼠肺组织IL-4含量无明显差异;1,8-桉油精30mg.kg-1也能降低哮喘豚鼠肺组织中ECP和TNF-α含量(P<0.01)。结论在哮喘急性发作时,1,8-桉油精通过减少嗜酸性粒细胞,下调嗜酸性粒细胞的活性,从而抑制了哮喘的急性发作。在哮喘迟发相阶段,1,8-桉油精可通过下调IL-8水平,降低TNF-α活性,从而抑制或改善由IL-8水平升高导致的中性粒细胞聚集于支气管肺泡而直接引起的哮喘加重和持续状态。     

Motorcycle Exhaust Particles Induce Airway Inflammation and Airway Hyperresponsiveness in BALB/C Mice

A number of large studies have reported that environmental pollutantsfrom fossil fuel combustion can cause deleterious effects tothe immune system, resulting in an allergic reaction leadingto respiratory tract damage. In this study, we investigatedthe effect of motorcycle exhaust particles (MEP), a major pollutantin the Taiwan urban area, on airway inflammation and airwayhyperresponsiveness in laboratory animals. BALB/c mice wereinstilled intratracheally (i.t.) with 1.2 mg/kg and 12 mg/kgof MEP, which was collected from two-stroke motorcycle engines.The mice were exposed 3 times i.t. with MEP, and various parametersfor airway inflammation and hyperresponsiveness were sequentiallyanalyzed. We found that MEP would induce airway and pulmonaryinflammation characterized by infiltration of eosinophils, neutrophils,lymphocytes, and macrophages in bronchoalveolar lavage fluid(BALF) and inflammatory cell infiltration in lung. In addition,MEP treatment enhanced BALF interleukin-4 (IL-4), IL-5, andinterferon-gamma (IFN-) cytokine levels and serum IgE production.Bronchial response measured by unrestrained plethysmographywith methacholine challenge showed that MEP treatment inducedairway hyperresponsiveness (AHR) in BALB/c mice. The chemicalcomponents in MEP were further fractionated with organic solvents,and we found that the benzene-extracted fraction exerts a similarbiological effect as seen with MEP, including airway inflammation,increased BALF IL-4, serum IgE production, and induction ofAHR. In conclusion, we present evidence showing that the filter-trappedparticles emitted from the unleaded-gasoline-fueled two-strokemotorcycle engine may induce proinflammatory and proallergicresponse profiles in the absence of exposure to allergen.     

枇杷叶提取物对卵清蛋白诱导的哮喘小鼠气道炎症和气道重塑的影响

目的 探究枇杷叶提取物对哮喘小鼠的治疗效果。方法 60只BALB/c小鼠随机分为6组,空白组,模型组,枇杷叶提取物低、中、高剂量组（50,100,150 mg·kg^-1）,地塞米松组（0.5 mg·kg^-1,阳性对照）。卵清蛋白（ovalbumin,OVA）诱导哮喘小鼠模型,各组小鼠分别灌胃给予相应药物。末次OVA造模后24 h吸入乙酰甲胆碱溶液检测小鼠气道高反应性。瑞氏-吉姆萨染色分类计数支气管肺泡灌洗液中炎症细胞数;ELISA检测Eotaxin、IL-4、IL-5、IL-13和OVA特异性IgE（OVA-specific IgE,OVA-sIgE）的水平;HE和AB-PAS染色观察小鼠肺组织的病理学改变;Western blotting检测肺组织中AKT、p-AKT、PI3K、Cyclin D1的蛋白表达。结果 枇杷叶提取物（100,150 mg·kg^-1）能有效减少炎性细胞包括嗜酸性粒细胞、巨噬细胞、淋巴细胞、中性粒细胞的数量;降低Eotaxin、IL-4、IL-5、IL-13和OVA-sIgE的表达水平;抑制哮喘小鼠肺组织炎症细胞的浸润和黏液分泌;抑制哮喘模型中AKT、p-AKT、PI3K、Cyclin D1的蛋白表达。结论 枇杷叶提取物对OVA诱导的哮喘气道炎症有良好的抑制效果,可为枇杷叶治疗哮喘的研究提供参考。     

分光光度法测定金蝉花中多糖的含量

目的建立金蝉花药材中多糖的含量测定方法.方法采用分光光度法测定多糖含量.结果金蝉花中多糖含量为24.16 mgg-1,平均回收率为97.37%,RSD＝2.34%,n＝5.结论本法简便、准确、灵敏、重现性好,为金蝉花药材的质量控制提供了依据.     

人工培养蛹虫草多糖的研究

以人工培养蛹虫草为原料 ,分离纯化得到蛹虫草多糖 (CMPS) ,经紫外扫描测定其为糖蛋白 .用凝胶过滤色谱法和聚丙烯酰胺凝胶电泳法验证了纯度 .测定了多糖的分子质量、糖含量和糖醛酸含量、单糖组成及摩尔比、蛋白含量及氨基酸组成、苷键构型等     

虫草多糖荧光标记的方法学研究

目的:对人工培养虫草多糖进行荧光标记,以供多糖的有关生物学研究.方法:先将多糖与酪胺反应,然后再与异硫氰酸荧光素(FITC)反应.对人工培养虫草多糖与酪胺反应中的反应时间、反应温度、pH、和酪胺用量进行了单因素考察.280nm的吸收峰表示多糖与酪胺的结合;450nm的吸收峰表示与FITC的结合.结果与结论:多糖荧光标记的最佳条件是:反应时间越长,温度在60℃,pH为8时反应率最高.其他多糖的荧光标记得出结构复杂的多糖,反应效率要低.     

虫草多糖对大鼠肾脏冷冻诱发慢性肾功能衰竭的治疗作用

目的：考察虫草多糖对肾脏冷冻诱发慢性肾功能衰竭大鼠的治疗作用。方法：通过冷冻肾脏复制大鼠慢性肾功能衰竭模型。将实验动物随机分成6组，在造模后第8周，各组大鼠开始给药（每日1次，连续14天），阳性对照组大鼠肌肉注射地塞米松磷酸钠0．1mg/kg，虫草多糖高、中、低剂量组大鼠灌胃给予虫草多糖160、80及40mg/kg。假手术组和阴性模型组大鼠灌胃给予等量生理盐水。检测给药后各组大鼠的血液生化指标、血清总超氧化物歧化酶和丙二醛含量以及肾脏病理学变化。结果：给药2周后，与阴性模型组比较，阳性对照组和虫草多糖3个剂量组大鼠血清尿素氮、肌酐、钠和磷含量以及血清丙二醛含量显著降低（P〈0．05或P〈0．01），而血清白蛋白和总超氮化物歧化酶含量显著增加（P〈0．05）；与阳性对照组比较，虫草多糖中、高剂量组大鼠血清总超氧化物歧化酶和丙二醛含量有显著差异（P〈0．05）或P〈0．01）；阳性对照组和虫草多糖高剂量组大鼠肾脏病理损伤明显好转，虫草多糖中、低剂量组则有所好转。结论：虫草多糖能有效预防慢性肾功能衰竭的发生和发展，改善肾功能，纠正代谢紊乱，促进肾单位的修复与再生。     

Ovalbumin-Induced Airway Inflammation and Fibrosis in Mice Also Exposed to Ozone

A murine model of allergen-induced airway inflammation was used to examine the effects of exposure to ozone on airway inflammation and remodeling. Sensitized BALB/c mice were exposed to ovalbumin aerosol for 4 wk before and after 2 wk of exposure to either 0.2 ppm or 0.5 ppm ozone. Other groups of mice were exposed to ovalbumin aerosol for 6 wk with continuous concurrent exposure to ozone during wk 1–6, or during intermittent concurrent exposure to ozone. Lung inflammation was measured by quantitative differential evaluation of lung lavage cells and by histological evaluation of stained lung sections. Alterations in lung structure (airway fibrosis) were evaluated by quantitative biochemical analysis of microdissected airways. The same total number of cells was observed in lavage fluid from animals exposed for 4 wk to ovalbumin alone or to ovalbumin for 4 wk immediately before or after exposure to 2 wk of 0.2 or 0.5 ppm ozone. Mice exposed to ovalbumin for 6 wk with concurrent exposure to either 0.2 ppm or 0.5 ppm ozone during wk 3–6 had a significant decrease in the total number of cells recovered by lavage. Values as low as 7% of the cell number found in mice exposed to ovalbumin aerosol alone were observed in the mice exposed to ovalbumin plus 0.2 ppm ozone during wk 3–6. There were significant differences in the cell differential counts in the lavage fluid from mice exposed to ovalbumin alone as compared with values from mice exposed to ovalbumin and ozone under all of the protocols studied. When ozone was given for 2 wk prior to ovalbumin exposure (Experiment 1), there were a high percentage of macrophages and low percentages of lymphocytes and eosinophils in the lung lavage. When ozone was given for 2 wk after ovalbumin exposure (Experiment 2), there were a moderate percentage of macrophages, a low percentage of eosinophils, and a high percentage of lymphocytes in the lung lavage. When ozone and ovalbumin were given simultaneously (Experiments 3 and 4), there were a high percentage of macrophages in the lavage with 0.2 ppm ozone and a high percentage of eosinophils. Ozone appears to antagonize the specific inflammatory effects of ovalbumin exposure, especially when given before or during exposure to ovalbumin. Airway remodeling was examined by two different quantitative methods. None of the groups exposed concurrently to ovalbumin and ozone had a significant increase in airway collagen content as compared to the matched groups of mice exposed to ovalbumin alone. The findings were consistent with an additive response of mice to simultaneous exposure to ovalbumin and ozone. Ozone exposure alone for 6 wk did not affect the number of goblet cells in the airways, while mice exposed to ovalbumin aerosol alone for 6 wk had about 25% goblet cells in their conducting airways. Concurrent exposure to ovalbumin and 0.2 ppm ozone caused significant increases in goblet cells (to 43% of total cells) in the conducting airways of the exposed mice. We conclude that when mice with allergen-induced airway inflammation induced by ovalbumin are also exposed to ozone, the lung inflammatory response may be modified, but that this altered response is dependent on the sequence of exposure and the concentration of ozone to which they are exposed. At the concentrations of ozone tested, we did not see changes in airway fibrosis. However, goblet-cell hyperplasia appeared to be increased in mice exposed concurrently to ovalbumin and 0.2 ppm ozone.     

Improvement of Pulmonary Function by Oral Treatment with a VLA-4 Antagonist in a Mouse Asthmatic Model

We investigated in vivo efficacies of the newly synthesized VLA-4 antagonist Compound A {trans-4-[1-[[2,5-Dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid} on Ascaris antigen–induced airway inflammation and hyperresponsiveness in a murine asthmatic model. Oral administration of Compound A significantly inhibited eosinophil infiltration into BALF and airway hyperresponsiveness 48 h after the antigen challenge. Histologic analysis of the lung sections confirmed the BALF result and revealed suppression of edema and mucus hyperplasia at 8 and 48 h after the challenge, respectively. These findings clearly show that orally active Compound A has therapeutic potential for treatment of asthma.     

银杏内酯吸入剂对哮喘模型豚鼠气管嗜酸性粒细胞浸润的影响

目的:探讨银杏内酯吸入剂对哮喘模型豚鼠气道嗜酸性粒细胞浸润的影响。方法:将豚鼠随机分为7组,每组8只,分别为哮喘模型组,银杏内酯吸入剂低、中、高剂量组(剂量分别为5、10、20mg·kg-1),银杏内酯腹腔注射(ip)组(剂量为20mg·kg-1),地塞米松组(剂量为10mg·kg-1)和正常对照组,计数肺灌注液(BALF)和支气管中的嗜酸性粒细胞(EOS)数。结果:与正常对照组比较,模型组BALF中的EOS显著增多,银杏内酯吸入剂组可显著减少BALF和支气管中的EOS浸润数(P<0.05)。结论:银杏内酯吸入剂能对抗哮喘豚鼠气道嗜酸性粒细胞浸润,可作为治疗支气管哮喘的一种新方法。