芍药苷对卵蛋白诱导的哮喘小鼠气道炎症的影响

目的 研究芍药苷对哮喘模型小鼠气道高反应性和气道炎症的影响.方法 以卵蛋白(OVA)致敏和激发小鼠哮喘模型,予地塞米松和低、中、高剂量芍药苷灌胃.测定各组小鼠气道高反应性;检测肺泡灌洗液(BALF)中白细胞、嗜酸性粒细胞、中性粒细胞、淋巴细胞、单核细胞及嗜碱性粒细胞水平;HE染色观察肺部病理变化.结果 芍药苷可明显降低气道高反应性,缓解肺部炎症浸润水平.结论 芍药苷对哮喘小鼠气道高反应性和肺部炎症具有显著的拮抗作用.     

A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma

Asthma is an inflammatory disorder caused by airway exposures to allergens and chemical irritants. Studies focusing on immune, smooth muscle, and airway epithelial function revealed many aspects of the disease mechanism of asthma. However, the limited efficacies of immune-directed therapies suggest the involvement of additional mechanisms in asthmatic airway inflammation. TRPA1 is an irritant-sensing ion channel expressed in airway chemosensory nerves. TRPA1-activating stimuli such as cigarette smoke, chlorine, aldehydes, and scents are among the most prevalent triggers of asthma. Endogenous TRPA1 agonists, including reactive oxygen species and lipid peroxidation products, are potent drivers of allergen-induced airway inflammation in asthma. Here, we examined the role of TRPA1 in allergic asthma in the murine ovalbumin model. Strikingly, genetic ablation of TRPA1 inhibited allergen-induced leukocyte infiltration in the airways, reduced cytokine and mucus production, and almost completely abolished airway hyperreactivity to contractile stimuli. This phenotype is recapitulated by treatment of wild-type mice with HC-030031, a TRPA1 antagonist. HC-030031, when administered during airway allergen challenge, inhibited eosinophil infiltration and prevented the development of airway hyperreactivity. Trpa1^−/− mice displayed deficiencies in chemically and allergen-induced neuropeptide release in the airways, providing a potential explanation for the impaired inflammatory response. Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving asthmatic airway inflammation following inhaled allergen challenge. TRPA1 may represent a promising pharmacological target for the treatment of asthma and other allergic inflammatory conditions.     

Cold air provocation of airway hyperreactivity in patients with cystic fibrosis

Thirty-four patients with cystic fibrosis (CF) were assessed for baseline pulmonary functions before, and 5 and 15 minutes after cold air challenge (CACh). Most of the patients had no change in forced expiratory volume in 1 second (FEV1) and maximum expiratory flow at 25% vital capacity (Vmax25%VC) post-CACh. Five patients responded with reduced FEV1 and 13 with reduced Vmax25%VC. However, paradoxical increases were noted in 10 patients for FEV1 and in 5 for Vmax25%VC. Paradoxical responses were most frequent in patients with severe lung disease. The explanation for this variability may lie in the varying degrees of airway instability and volume of airway contribution (VAC) to early flows, resulting from the damage caused by chronic infection. Conventional challenges may be useless in determining the true incidence of bronchial hyperreactivity in patients with CF.     

Dexamethasone reduces tachykinin but not ACh airway hyperreactivity after 03

We investigated whether dexamethasone pretreatment affected the acute increase in airway reactivity produced by high-level ozone exposure. Reactivity to intravenous IV substance P (SP), IV acetylcholine (ACh), or aerosolized capsaicin (CAP) before and 1 hr after ozone exposure (3 ppm for 2 hr) was determined by measuring specific airway resistance in anesthetized, spontaneously breathing guinea pigs, half of whom had been pretreated for 2 days pre-ozone with dexamethasone (2 mg/kg intramuscularly [IM] daily). The amount of IV SP, IV ACh, or inhaled capsaicin necessary to increase baseline specific airway resistance by 100% (ED₂₀₀ACh or ED_2OOSP) or 35% (ED₁₃₅CAP) was determined by interpolation from dose-response curves. Compared to their pre-ozone status on the day of exposure, we found that dexamethasone-pretreated animals manifested significantly less of an increase in airway reactivity postozone to IV SP or inhaled CAP than did untreated animals. Changes in logEDs of the pretreated group were 0.18 ±0.03 (mean ± SE) for SP and 2.20 ± 0.11 for CAP compared to 0.27 ± 0.04 and 3.38 ± 0.34, respectively, for the untreated groups post-ozone (p < 0.05 and n = 4 for each). In contrast, dexamethasone pretreatment had no effect on IV ACh reactivity postozone: changes in logED_2OOACh were 0.27 ± 0.08 and 0.28 ± 0.04 for the pretreated and untreated groups, respectively (n = 4). In animals pretreated with captopril to block possible dexamethasone stimulation of angiotensin-converting enzyme synthesis that could influence tachykinin reactivity, we found that the corticosteroid effect on post-ozone SP reactivity was as marked as that seen in animals without captopril (n = 4). Because these reactivity studies were consistent with the possibility that dexamethasone may ameliorate ozone-induced, tachykinin hyperreactivity by stimulating airway neutral endopeptidase (NEP), we measured NEP activity by high-performance liquid chromatography (HPLC) of each tracheal homogenate made from other groups of animals. Homogenates from ozone-exposed, dexamethasone-pretreated animals demonstrated significantly greater NEP activity (81 ± 24%) than that from ozone-exposed, untreated animals (p < 0.05, n = 5). We conclude that corticosteroid pretreatment reduces the acute increase in airway reactivity to exogenous and endogenous tachykinins caused by ozone. This reduction may be at least partly due to stimulation of airway NEP activity, perhaps most of which is nonmucosal in that ozone acutely inactivates mucosal NEP. Offprint requests to: C. G. Murlas     

支气管结核患者的气道高反应性

目的研究支气管结核患者气道高反应性及肺通气功能状况,为早期确诊支气管结核,避免误诊提供客观依据。方法 2002年1月至2005年4月收集24例支气管结核患者,均经纤维支气管镜、胸部 CT、病理等多项检查证实,并进行肺功能测定,且对肺通气功能、气道阻力、气道反应性测定结果进行 t 检验及相关分析。结果高达41.7%的支气管结核患者存在气道高反应性,支气管结核患者还有剧烈咳嗽(100%,24/24)、呼吸困难(54%,13/24)、喘息等症状,而有血痰者仅占21%(5/24),因此极易被误诊为支气管哮喘,特别是咳嗽变异性哮喘。伴有气道高反应性的支气管结核患者的第一秒用力呼气容积占预计值百分比(FEV_1占预计值%)为(80.8±14.1)%,高于未伴有气道高反应性者的(65.8±16.4)%,差异有统计学意义(t=2.345,P<0.05),两组间比较,第一秒用力呼气容积与用力肺活量比值(FEV_1/FVC)、最大呼气中段流量(MMEF)、用力呼出25%肺活量时呼气流量(V_(75%))和气道阻力的差异无统计学意义(t 值为0.506～1.391,P 均>0.05)。伴有气道高反应性的支气管结核患者中,气道高反应性的高低仅与 FEV_1占预计值%呈负相关(r=-0.61,P<0.05),与其他肺功能指标均无明显相关。推测支气管结核患者气道高反应性的形成可能与其气道慢性炎症或刺激受体的暴露有关。结论支气管结核患者的气道高反应性不可忽视,应注意与咳嗽变异性哮喘鉴别。     

地塞米松对支气管哮喘豚鼠白介素4、白介素5及气道反应性的影响

目的 探讨地塞米松对支气管哮喘(简称哮喘)豚鼠模型白介素4(IL-4)、IL-5水平及气道高反应性(airway hyperreactivity,AHR)的影响,为激素治疗哮喘提供理论依据.方法 实验分为3组:正常对照组、哮喘模型组和地塞米松治疗组,每组各10只豚鼠.用卵白蛋白腹腔注射致敏和雾化吸入激发建立哮喘豚鼠模型,三通管做气管插管进行机械通气,测定气道内压力以反映气道反应性,酶联免疫吸附试验(ELISA)检测豚鼠血清中IL-4、IL-5含量.结果 哮喘模型组豚鼠血清IL-4、IL-5含量,分别为(38.2±3.4)ng/L和(344.4±21.8)ng/L,显著高于正常对照组,分别为(19.8±1.2)ng/L和(77.8±26.0)ng/L(P＜0.01);地塞米松组IL-4、IL-5含量,分别为(22.0±1.8) ng/L和(234.6±35.1)ng/L,均明显低于哮喘模型组(P＜0.01).哮喘豚鼠模型组气道反应性(0.013±0.014) g/L与正常对照组(0.168±0.186) g/L比较显著升高(P＜0.01);地塞米松组气道反应性(0.144±0.154) g/L与哮喘模型组比较显著降低(P＜0.01),与正常对照组比较差异无统计学意义(P＞0.05).结论 地塞米松能有效降低哮喘豚鼠AHR,其机制可能是抑制哮喘豚鼠体内IL-4、IL-5的生成.     

High-frequency electrical stimulation of cervical vagi reduces airway response to methacholine

AIM: To test whether high-frequency electrical stimulation (HES) of the bilateral cervical vagus nerves reduces the airway responses to methacholine (MCh). METHODS: Guinea pigs were pretreated with saline (Sal, n = 9) or ovalbumin (Ova, n = 10) aerosol for two weeks (5 min/d, 5 d/wk) and subsequently anesthetized, paralyzed, tracheotomized and artificially ventilated. Both total lung resistance (R_L) and dynamic pulmonary compliance (C_dyn) were recorded. In addition, the effects of vagal low-frequency electrical stimulation (LES, monophasic, 50 Hz) and HES (monophasic and biphasic, 1 and 2.5 kHz) for about 10 s or 2 min on the responses of R_L and C_dyn to MCh aerosol-induced bronchoconstriction were compared in both groups of guinea pigs. In a few guinea pigs, the impact of bivagotomy on the R_L responses to MCh was assessed. RESULTS: Before MCh challenge, LES, but not HES, significantly increased R_L by about 30% (P < 0.01) and decreased C_dyn by about 20% (P < 0.01) similarly in both groups. MCh aerosol for 2 min elevated R_L and diminished C_dyn more in Ova- than Sal-treated animals (R_L: 313% ± 52% vs 113% ± 17%, P < 0.01; C_dyn: -56% ± 7% vs -21% ± 3%, P < 0.01). During MCh-induced airway constriction, LES further enhanced, but HES decreased R_L and this decrease was greater in Ova- (about 45%) than Sal-treated animals (about 34%, P < 0.01) with little change in cardiovascular activity. On the other hand, LES further reduced whereas HES increased C_dyn more in Ova- (about 20%) than Sal-treated animals (about 13%, P < 0.01). In addition, bivagotomy almost eliminated the R_L and C_dyn responses to MCh. CONCLUSION: We conclude that vagal HES is able to alleviate the bronchoconstriction induced by MCh in anesthetized guinea pigs, likely via reversible inhibition/blockade of vagal conduction.     

Inherent and antigen-induced airway hyperreactivity in NC mice

In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sensitization to and challenge with antigen induced accumulation of inflammatory cells, especially eosinophils, in lung and increased airway reactivity in NC and BALB/c mice. These results indicate that NC mice exhibit inherent and antigen-induced airway hyperreactivity. Therefore, NC mice are a suitable strain to use in investigating the mechanisms underlying airway hyperreactivity and such studies will provide beneficial information for understanding the pathophysiology of asthma.     

细胞周期蛋白D1在支气管哮喘小鼠肺组织中的表达及其与气道重塑的关系

目的 研究细胞周期蛋白D1(Cyclin D1)在支气管哮喘(简称哮喘)小鼠肺组织中的表达,探讨Cyclin D1在哮喘及气道重塑中的作用.方法 将40只SPF级BALB/c小鼠按随机数字表法分为正常对照组(A组)、哮喘雾化2周组(B组)、哮喘雾化4周组(C组)、哮喘雾化8周组(D组)4组,每组10只.用10%鸡卵白蛋白(OVA)致敏和1%OVA激发小鼠建立哮喘模型.分析支气管肺泡灌洗液(BALF)中嗜酸粒细胞(EOS)计数及分类;用动物肺功能仪检测各组小鼠肺功能状况;用苏木精-伊红(HE)染色观察气道炎症及细胞浸润情况;用图像分析软件观察气道壁及平滑肌层变化情况;用逆转录-聚合酶链反应(RT-PCR)及实时定量(Real-time)PCR测定肺组织中Cyclin D1 mRNA水平表达变化;用Western blot法观察肺组织中Cyclin D1的蛋白表达变化.结果 BALF分析结果提示,B、C、D组EOS计数分别为(42.6±0.9)×104/L、(54.7±1.4)×104/L、(44.8±2.4)×104/L,与A组[(3.4±0.5)×104/L]比较差异有统计学意义(q值分别为79.75、91.42、84.82,P均＜0.01);对小鼠呼气阻力检测发现,乙酰胆碱浓度为45 μg/kg时B、C、D组分别为(5.27±0.16)cm·L-1·min-1、(6.68士0.20)cm·L-1·min-1、(7.14±0.41)cm·L-1·min-1,与A组[(4.11±0.15)cm·L-1·min-1]比较差异有统计学意义(q值分别为5.58、6.39、7.11,P均＜0.05);支气管平滑肌面积/管腔内周长(Wam/Pi)B组为2.8±0.6,C组为4.8±0.6,D组为6.4±0.7,与A组(2.4±0.4)比较差异有统计学意义(q值分别为6.40、8.28、9.27,P＜0.05);管壁面积/管腔内周长(Wat/Pi)B组为6.4±0.8,C组为8.3±1.2,D组为9.3±1.0,与A组(5.6±1.0)比较差异有统计学意义(q值分别为2.80、4.83、6.37,P均＜0.05);Western blot检测发现Cyclin D1在B、C、D组表达量分别为0.587±0.015、0.808±0.029、0.826±0.022,与A组(0.404±0.016)比较差异有统计学意义(q值分别为5.87、8.08、8.26,P均＜0.01);相关性分析结果提示呼气阻力和Cyclin D1水平表达呈正相关(r=0.83,P＜0.05).结论 Cyclin D1在哮喘小鼠肺组织中表达增加,其表达与气道反应性呈正相关,Cyclin D1可能通过细胞外信号调节激酶(ERK)信号通路参与气道重塑过程.     

T-cell-mediated induction of airway hyperreactivity in mice.

Airway hyperreactivity is an almost universal feature of asthma. The origin of this phenomenon is poorly understood. Although a role has been suggested for cell-mediated immune responses in the induction of bronchial hyperreactivity, direct evidence for such a role is not available. In the present study it was investigated whether delayed-type hypersensitivity (DTH) to picryl chloride (PCI) in mice used as a model for cellular immunity can induce airway hyperreactivity. DTH infiltrates in the lungs of PCI-sensitized and challenged BALB/c mice occurred at 24 h after challenge, and they were maximal at 48 h. The inflammatory infiltrate resolved gradually and disappeared completely after 14 days. Whether or not the DTH-like inflammatory reaction influenced lung function parameters was tested in vivo. From these experiments it was concluded that the pulmonary resistance in mice with a DTH-like inflammation was increased. Dynamic compliance was unchanged. In PCI-sensitized and challenged BALB/c mice, hyperreactivity of isolated trachea to carbachol was found at 2 h after challenge. It was maximal at 48 h after challenge and lasted for at least 3 wk. The response was antigen-specific. Moreover, the phenomenon was T-cell-dependent since in athymic (nude) mice no hyperreactivity to carbachol was detected. In addition, hyperreactivity could be observed after challenge of mice that were passively sensitized by intravenous injection of lymphoid cells from sensitized donor mice. After T-cell depletion of the donor lymphoid cells, the hyperreactivity to carbachol was significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cough induced by airway vibration as a model of airway hyperreactivity in patients with acute upper respiratory tract infection

Patients with acute upper respiratory tract infection (URTI) have been shown to be hyperreactive to inhaled tussigens such as citric acid and capsaicin, and the authors propose that this may be due to an increased sensitivity of airway receptors that mediate cough. In recent studies we have demonstrated that cough may be induced by vibration of the airway at the level of the throat or chest in patients with URTI but that the same stimuli induce little or no cough in healthy subjects. The difference between the patients with URTI and healthy subjects in their response to airway vibration may be explained on the basis of hyperreactivity of airway sensory receptors. We propose that the model of cough induced by airway vibration may be useful for studies on the pathophysiology and pharmacology of airway hyperreactivity in acute cough. The airway vibration model of cough may have some advantages over inhaled tussigens as the stimulus is easily controlled and the method is safe for use in children.     

Prevention of bronchial hyperreactivity in children

Hyperresponsiveness of the bronchi is defined as an excessive reaction of bronchial mucosa to irritants that do no harm to a healthy mucosa. Measures to prevent bronchial hyperreactivity in children with asthma and other diseases remain rather ineffective at present. Though progress has been made in some areas.     

Determinants and regulating processes in bronchial hyperreactivity

Bronchial hyperresponsiveness (BHR) can be considered as a feature of asthma, although only a loose relationship is present with symptoms and severity of the disease. Epidemiology of BHR may inform about determining factors in BHR and its role as a risk factor. BHR is found already at a young age, mostly diminishes with age, and increases in many asthmatic patients after midlife. Genetic determinants are suggested by familial segregation and twin studies. Allergy, respiratory infections, and cigarette smoking are found to induce increase in BHR and to modify its degree at the long run. The mechanisms in BHR are being unraveled gradually. A chronic inflammation with an important role for eosinophils, mast cells, and others, is thought to modify bronchial mechanisms, such as smooth muscle, epithelium, and autonomic systems. Growing evidence supports that T lymphocytes are implicated and may determine many of the inflammatory cells, such as eosinophils, neutrophils, and mast cells.     

Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluid in rats

Melatonin is a free radical scavenger with potent antioxidant properties and immunomodulatory effects. The purpose of this study was to determine the effects of orally administered melatonin in a pancreatic fluid (PF)-induced lung inflammation and airway hyperreactivity model. Aerosolized PF was introduced into airways to induce inflammation in rats. Animals were randomized into three experimental groups: sham treated; PF treated (200 μL/kg); and PF with melatonin (10 mg/kg) pretreatment. Airway reactivity to methacholine, airflow and airway resistance, bronchoalveolar lavage (BAL) cellular differential, the tumor necrosis factor α (TNFα) level, lavage nitric oxide, hydroxyl radical, and lactic dehydrogenase (LDH) were compared among groups. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFα in lung tissues were determined by real-time polymerase chain reaction. Protein expressions of iNOS and nitrotyrosine and lung tissue myeloperoxidase (MPO) activity were determined using an ELISA assay. Oral melatonin treatment indicated anti-inflammatory efficacy as evidenced by decreased methacholine sensitivity by 24% and airway obstruction by 28%, reduction in BAL eosinophil (P < 0.01) and neutrophil counts (P < 0.05), LDH (P < 0.05), and TNFα concentrations (P < 0.05) when compared to levels in sham-treated rats. Melatonin-treated animals also had reduced nitric oxide and hydroxyl radical concentrations (P < 0.05) in lavage fluid. Oral melatonin significantly reduced mRNA and protein expression of iNOS (P < 0.05 and P < 0.01, respectively), TNFα (P < 0.05), nitrotyrosine (P < 0.05), and MPO activity (P < 0.05) in lung tissues when compared with the sham-treated animals. These results suggest that oral treatment with melatonin had a beneficial effect on PF-induced obstructive ventilatory insufficiency by attenuating nitrosative and oxidative stress.     

苦参碱对支气管哮喘小鼠气道炎症和早期气道重塑的影响

目的 观察苦参碱对支气管哮喘(简称哮喘)小鼠早期气道重塑和炎症的影响.方法 将50只BALB/C小鼠按随机数字表法分为空白对照组(A)、哮喘模型组(B)、地塞米松组(C)、苦参碱高剂量组(D,50 mg/kg)和低剂量组(E,25 mg/kg)5组.卵清白蛋白致敏建立哮喘小鼠模型,每次激发前,C、D、E组分别给予地塞米松和相应剂量的苦参碱进行灌胃;B组给予等剂量生理盐水;A组以等剂量的生理盐水致敏、激发及灌胃.肺组织切片染色,炎症细胞及黏液分泌评分、定量杯状细胞百分比,测定平滑肌面积、基底膜胶原面积.采用逆转录PCR和免疫组织化学检测转化生长因子-β1(TGF-β1)和结缔组织生长因子(CTGF)的Mrna和蛋白表达水平.采用SPSS 13.0统计软件处理,符合正态分布和方差齐性的数据采用单因素方差分析(one-way ANOVA),多组间两两比较采用Dunnet-t检验;对等级数据和不符合正态分布或方差齐性的数据则进行秩和检验(Kruskal-Wallis法),多组间两两比较采用Mann-whiteney检验;相关性采用Spearman等级相关分析.结果 A-E组炎症细胞评分(均数,四分位数)分别为1.5(1,2)、4(4,5)、2(1,3)、2(2,3)、3(2,3.3),黏液分泌评分分别为1.5(1,2)、5(4,6)、2(1,3)、2(2.5,4)、3(3,4),B组明显高于A组(X2值分别为21.3和22.6,均P<0.01),C组明显低于B组(X2值分别为13.3和15.0,均P<0.01),D、E组低于B组(X2值分别为9.1、10.9和9.8、9.7,均P<0.05);杯状细胞占上皮细胞百分比分别为(1.7±0.5)%、(54.7±15.5)%、(20.4±5.9)%、(31.7±7.6)%、(36.2±10.8)%,B组明显高于A组(t=12.0,P<0.01),C、D组明显低于B组(t值分别为7.7和5.1,均P<0.01),E组低于B组(t=4.2,P<0.05);5组平滑肌面积分别为(11.5±2.1)、(30.0±3.3)、(15.2±3.1)、(22.2±4.8)和(26.5±3.4)um2/um,B组明显高于A组(t=11.4,P<0.01),C、D、E组均明显低于B组(t值分别为9.1、4.7和2.2,均P<0.01);胶原沉积面积5组分别为(3.9±1.8)、(24.4±6.1)、(15.4±3.5)、(16.6±6.0)和(17.5±4.4)um2/um,B组明显高于A组(t=9.3,P<0.01),C、D组明显低于B组(t值分别为4.1、3.5,均P<0.01),E组低于B组(t=3.2,P<0.05);5组TGF-β1 Mrna灰度值分别为160±25、247±37、174±23、195±25、207±42,CTGF Mrna灰度值5组分别为86±8、160±24、94±10、93±14、104 4-10,B组明显高于A组(f值分别为6.1、11.6,均P<0.01),C、D、E组均明显低于B组(t值分别为3.7、2.7、5.1和10.6、8.6、10.3,均P<0.01).5组肺组织TGF-B1吸光度值分别为21±5、36±8、26±5、26±5和26±5,肺组织CTGF吸光度值分别为15±4、27±5、21±4、22±3和23±4,B组明显高于A组(t值分别为5.7和6.4,均P<0.01),c、D组明显低于B组(t值分别为3.9、3.9和3.2、2.8,均P<0.01),E组低于B组(t值分别为3.8和2.5,均P<0.05).各组小鼠胞质中TGF-β1与平滑肌面积、TGF-β1与胶原沉积面积、CTGF与平滑肌面积、CTGF与胶原沉积面积均呈正相关(r值分别为0.435、0.583、0.522和0.590,均P<0.01).结论 苦参碱能够抑制哮喘的早期气道重塑和炎症,其抑制气道重塑的可能机制与TGF-β1到CTGF的信号转导通路有关.     

钙池操纵性钙通道抑制剂SKF96365对慢性哮喘小鼠气道重塑和气道高反应性的作用

目的:观察钙池操纵性钙通道抑制剂SKF96365对小鼠慢性哮喘模型气道重塑和气道高反应性的影响。方法:用鸡卵清白蛋白(OVA)致敏和激发小鼠,建立慢性哮喘模型,33只雌性BALB/c小鼠随机分为3组:对照组、哮喘组、SKF96365组,每组11只,其中SKF96365组于每次激发前30 min给予SKF96365(10mg/kg)干预。哮喘组和SKF96365组于第0、7、14 d腹腔注射(i.p)200μL致敏液(含OVA粉剂20μg、氢氧化铝凝胶2 mg);自第21天起,腹腔注射1%戊巴比妥钠(70mg戊巴比妥钠/kg小鼠体重)麻醉小鼠后,OVA(40μg)滴鼻(i.n),连续6周,每周3次,共18次。对照组则在相同时间给予相应剂量的生理盐水腹腔注射和滴鼻。最后一次激发后24 h,各组分别随机取5只小鼠用于检测组织病理学变化,另6只小鼠采用Buxco小动物肺功能仪检测气道高反应性。其中组织病理学检测计算杯状细胞(过碘酸希夫染色阳性,PAS+)、胶原细胞(Masson阳性)和平滑肌细胞(α-SMA阳性)阳染面积/支气管基底膜周长值来评估小鼠气道重塑;观察给予不同浓度乙酰甲胆碱雾化时的气道阻力(resistance index,RI)最大值,评估小鼠气道高反应性。结果:对照组未见PAS阳性染色区域,哮喘组和SKF96365组杯状细胞增生高于对照组(7.29±2.04,4.49±1.70 vs 0.00±0.00,均P0.01),且SKF96365组低于哮喘组(P0.05)。Masson染色显示哮喘组和SKF96365组上皮下胶原沉积高于对照组(9.23±1.41,7.30±1.33 vs 1.60±0.77,均P0.01),且SKF96365组低于哮喘组(P0.05)。α-SMA免疫组化显示哮喘组和SKF96365组平滑肌增生肥大高于对照组(4.54±1.05,3.15±0.57 vs 1.97±0.69,均P0.05),且SKF96365组低于哮喘组(P0.05)。当乙酰甲胆碱(Mch)≤6.25 mg/m L时,3组小鼠气道阻力无显著差异(P0.05),当25 mg/m LMch≥12.25 mg/m L时,哮喘组小鼠气道阻力明显大于对照组小鼠(P0.001),当Mch≥25 mg/m L时,哮喘组小鼠气道阻力大于SKF96365组(P0.05)。结论:采用SKF96365干预后,慢性哮喘小鼠气道重塑和气道高反应性指标均有改善,提示SKF96365可能对哮喘气道重塑和气道高反应性具有抑制作用。     

布地奈德干预对卵白蛋白致敏小鼠抗原激发后气道炎症及气道重塑的影响

目的　观察早期及延迟应用布地奈德对支气管哮喘 (简称哮喘 )小鼠气道炎症和气道重塑的防治作用。方法　40只小鼠分为 5组,每组 8只。鸡卵白蛋白(OVA)致敏 /激发组 (A组 ),生理盐水对照组(B组),布地奈德 (BUD)早期治疗组 (C组 ),BUD延迟治疗组 (D组 ),OVA延迟对照组(E组)。小鼠于第 0、14天以OVA致敏,从第 1次致敏后第 24天开始雾化吸入 2.5%的OVA激发并持续 18d,建立气道重塑模型;分别在早期(抗原激发前 1d始)和延迟(第 1次抗原激发后第 18天始)雾化吸入BUD(0.5mg/ml),观察抗原激发及BUD应用后支气管肺泡灌洗液(BALF)中嗜酸粒细胞(EOS)数、上清液白细胞介素 5(IL-5)和γ干扰素 (IFN-γ)水平的变化,同时对肺组织切片行苏木精 伊红(HE)、过碘酸雪夫(PAS)、Masson三色染色,测定支气管壁周围EOS计数、定量杯状细胞百分比及黏液分泌评分并测定气道平滑肌增生高度及胶原面积。结果　经过反复抗原激发,A组BALF中EOS数为(57.460±11 060)×104 /ml,B组为[ (0.050±0.020)×104 /ml],两组比较差异有统计学意义(P<0.01);A组BALF中IL- 5水平及IFN -γ水平分别为(52.9±2.8)pg/ml、(39.5±3.2)pg/ml,B组分别为(16.8±1.5)pg/ml、(63.8±3.3)pg/ml,两组比较差异有统计学意义 (P<0.01 );A、B组支气管壁周围EOS数分别     

二尖瓣狭窄患者气道高反应性与糖皮质激素吸入的治疗 …

目的 了解气道反应性增高和二尖瓣狭窄患者咳嗽及气短症状间的关系,以及糖皮质激素吸入的治疗作用。方法 测定２３例二尖瓣狭窄患者的气道反应性,对１５例（６５％）气道反应性增高者,随机分为丙酸倍氯米松治疗组（８例）和安慰剂组（７例）,治疗６周后复查。治疗前后测定患者咳嗽及气短症状评分。对８名气道反应性正常者亦吸入丙酸倍氯米松作为对照组。结果 丙酸倍氯米松吸入组治疗６周后,其气道反应性显著降低（Ｐ〈０．０