马类动物气喘病病理研究：35例自然病畜病性与病理

用HE及特殊染色法、电镜、能谱分析、电子探针、偏光显微镜及微生物分离培养等方法,研究了气喘病自然病例的肺与支气管淋巴结。肺与淋巴结组织中尘细胞明显增多,细胞器受损,铝、硅等元素超常,肺组织变化还包括单核细胞性肺泡炎和间质性肺炎,从病肺中分到了普通高温放线菌、干草小多孢菌等菌类。结果表明,肺中有机与无机成分均存在。作者认为,甘肃河西一带的马类动物气喘病属一种极少报告的外源性混合性尘肺,其中,有机尘肺与国外描述的“马农民肺”(farmer's lung of horses)变化相似。     

麦草土尘致家兔尘肺的病理学研究

用甘肃河西地区麦草土尘在家兔成功地复制出了尘肺模型,病理形态学研究表明,在肺与支气管淋巴结可引起尘沉着和尘细胞结节形成,引起支气管炎和血管周炎,单核细胞肺泡炎和间质性肺炎,淋巴结构的尘细胞结节形成等。这些变化与甘肃河西地区马类动物气喘病自然病例的变化相似。病理生理学研究表明,试验组动物有较严重的低氧血症和呼吸性酸中毒,肺循环中有大量单核细胞和微血栓滞留,试验后期肺组织顺应性明显降低,这也是引起尘肺     

甘肃省马气喘病研究—家兔和豚鼠的农民肺模型

用从甘肃省马气喘病自然病例肺中分得的5株放线菌和5株霉菌,对34只家兔和23只豚鼠进行了实检性农民肺研究。通过吸入与气管内注入上述菌粉,在这些动物中首次成功地复制出农民肺模型。染菌动物的症状与病变同在气喘病马所看到的很相似。尸检时见肺膨大、气肿,还有密散的结节。镜检动物的肺组织,观察到单核巨噬细胞性肺泡炎、间质性肺炎、支气管周炎与上皮样-巨细胞肉芽肿形成,但豚鼠比家兔的淋巴网状组织增生更明显。结果表明,所分得的霉菌和放线菌包括热吸水链霉菌参与了甘肃马农民肺的病理发生。     

马类动物气喘病病理研究——家兔实验性麦衣土尘肺的病理模型

甘肃农大兽医系的研究结果表明,甘肃河西一带马类动物气喘病是由外界吸入的无机尘与有机尘所致的混合性尘肺,无机尘主要是存在于家畜外界环境中的麦衣土尘。本试验是为了确证麦衣土尘能否在家兔引起尘肺病变及其和自然病例病变的相似性。     

甘肃省河西地区马类动物气喘病微生物学检查

本研究从35例气喘病马类动物中分离出与气喘病发生有关的微生物有普通高温放线菌、普通高温放线菌橙色变种、热吸水链霉菌、干草小多孢菌、构巢曲霉、桔青霉、局限青霉、杂色曲霉、禾谷镰刀菌、短密青霉、高大毛霉以及副流感3型。其中以嗜热放线菌类为主,并以9头健康马类动物和牲畜的饲草饲料中也分离到嗜热放线菌类和毛霉、青霉、曲霉等。试验证明,这些微生物在自然界分布广泛,而病畜体内菌检率较健畜为高。除了杂色曲霉和构巢曲霉外,其它在国内尚未见有在马类动物气喘病中分离的报道,而热吸水链霉菌在国外也未见报道。     

电子探针X射线微分析仪对马属动物气喘病病变组织的研究

对8例气喘病畜的肺和支气管淋巴结进行了矿物分析,证实这两个器官的组织中含有比同类健康家畜高得多的铝、硅等无机元素,其组成的矿物主要是铝硅酸盐,也有二氧化硅(石英)。这一结论为本病因之一——无机尘性质的确定提供了可靠的依据。     

马类动物气喘病血液学值的变化

<正> 甘肃省马类动物气喘病是一种以呼吸困难、气喘和咳嗽为主要症状的呼吸系统疾病,主要分布于河西走廊一带。甘肃农业大学近年来的研究确定,本病是由有机尘和无机尘共同作用所致的一种混合性尘肺。有机尘主要包括普通嗜热放线菌(Thermoactinomyces vulgaris)和干草小多孢菌(Micropolyspora faeni),无机尘主要是来自外界的土尘(铝硅酸盐类矿物)。血液学检验在许多疾病的诊断上都具有重要意义,马气喘病也不例外。在本病的研究中,我们对126例自然病例和临诊病例进行了全面系统的检查和血液学检验,现报告如下。     

中西结合治疗马属动物气喘病

中西结合治疗马属动物气喘病张英王凯（青海省畜牧科技信息咨询站８１０００８）（青海畜牧兽医学院）马属动物气喘病是有机尘和无机尘引起的混合性尘肺,是马属家畜以气喘为主要临床症状的呼吸系统疾病。国外研究认为,该病与霉菌性过敏性变态反应有关。我国甘肃、云南、...     

马类动物气喘病病理研究——“马农民肺”病理模型的复制

甘肃河西地区马气喘病是否由“农民肺”的那些病原引起,早已被有些研究者注意。我系马气喘病研究课题组近年来进行了大量调查和研究工作,并陆续从自然病例的肺组     

普通高温放线菌与饲草土尘致家兔实验性尘肺的研究

用从饲草中分得的土尘和从甘肃河西地区气喘病马肺中分到的一株普通高温放线菌(Thermoactinomyces vulgaris——T.v.),对50只家兔进行了实验性尘肺的研究。从病理形态可见,只有在土尘和菌尘先后感染或同时感染后其病理学改变才与河西地区马气喘病自然病例的病变更为相似。电镜检查,在实验兔肺泡巨噬细胞内可见到尘粒和T.v.孢子残骸。CIEP和ELISA检测,在染菌3次以上实验兔血清中检出了沉淀素抗体和循环免疫复合物。免疫荧光技术查明在肺组织内有T.v.孢子和IgG沉着。结果表明,在混合性尘肺的发病机理中,土尘和普通高温放线菌存在相互协同的关系,且尘肺的发生是机体对土尘所致肺泡损伤的非特异修复及对这种放线菌孢子侵害发生Ⅰ、Ⅳ型变态反应所引起的。     

双峰驼尘肺研究

用光镜、电镜、电子探针微分析仪及原子发射光谱仪（ＩＣＰ）等，对内蒙古阿拉善右旗和甘肃民勤县的共４８例双峰驼的肺脏、支气管淋巴结及纵隔淋巴结进行了研究。结果表明，４８例的支气管淋巴结和纵隔淋巴结均有程度不等的尘沉着变化，其中１３例肺脏有程度不等的尘肺病变。肺脏的尘肺病变主要为局灶型，尘灶与尘细胞结节呈星散状分布，多位于细支管周围、肺泡隔和肺胸膜结缔组织。病变部常有程度不等的慢性炎症，少数病例发生灶性纤维化。电镜观察发现，淋巴结中，尘细胞的线粒体空泡化，内质网扩张，尘粒积聚体处细胞器完全破坏。元素分析表明，肺和淋巴结中的粉尘多为铝硅酸盐类化合物。作者认为，双峰驼铝硅酸盐尘肺的发生同该地区大气环境浮尘含量过高有关。但骆驼尘肺的病变比马的轻，这主要与骆驼呼吸道和肺脏有较完善的除尘机构有关。     

Cytokine mRNA expression of pulmonary macrophages varies with challenge but not with disease state in horses with heaves or in controls

Heaves in horses is characterized by lower airway neutrophilic inflammation, and reversible airflow obstruction. Pulmonary macrophages contribute to the inflammation observed in a number of human and animal pulmonary diseases, and it has been postulated that they are responsible for the neutrophilic inflammation present in heaves by the release of cytokines and chemokines. To test this hypothesis, the mRNA expression of TNF-α, IL-1β, IL-8, and MIP-2 by macrophages isolated from bronchoalveolar lavage cells was quantified using real-time RT-PCR in horses with heaves (n-6) and controls (n-6). Animals were studied after being pastured for 3 months to induce clinical remission of heaves, and after 24h, and 9 days of a continuous natural antigen challenge consisting of hay feeding and straw bedding. The study was performed during 2 consecutive summers, when 3 horses with heaves and 3 control horses were evaluated. As expected, airway obstruction developed with the challenge only in horses with heaves, while airway neutrophilia was observed in both groups of horses. Stabling resulted in an increased expression of IL-8/?-actin and MIP-2/?-actin after 24h of stabling in both groups of horses. Further analyses revealed that compared to pasture, the expression of these chemokines was significantly increased after 24h of stabling only in Year 1, while the IL-8 expression was significantly decreased at 9 days in Year 2. No significant group, time, or year differences in IL-1β/?-actin and TNF-α/?-actin ratio were observed. The expression of IL-1β was strongly correlated with neutrophil percentages, although at different time points in the two study-years. These results suggest that alveolar macrophages can contribute to the airway inflammation resulting from stabling in horses by the release of IL-8 and MIP-2, but that the release of these chemokines is unlikely to be responsible for the marked airway neutrophilia observed in heaves. The variable expression of IL-8 and MIP-2 by alveolar macrophages between the two-study years are additional novel findings highlighting the complexity of the inflammatory pathways associated with airway inflammation and the importance of evaluating concurrently horses with heaves and controls to ensure identical environmental challenges.     

Pulmonary distribution of aerosolized technetium Tc 99m pentetate after administration of a single dose of aerosolized albuterol sulfate in horses with recurrent airway obstruction.

OBJECTIVE: To determine whether pulmonary distribution of aerosolized technetium Tc 99m pentetate is improved after inhalation of a single dose of albuterol sulfate in horses susceptible to recurrent airway obstruction (heaves). ANIMALS: 6 horses with heaves and 4 horses with normal respiratory tract function. PROCEDURE: Images were obtained during ventilation of horses at baseline (maximal change in pleural pressure during tidal breathing [deltaPpImax] >15 cm H2O) and after aerosolized albuterol sulfate (360 microg) administration, with a 24-hour washout period between experiments. The deltaPpImax was determined prior to the baseline scan, prior to albuterol sulfate administration, and 5 minutes after albuterol sulfate administration. Images were assessed by visual inspection (semi-quantitative scoring system) and histogram analysis. RESULTS: Images obtained from horses with heaves had nonuniform pulmonary distribution of radionuclide characterized by poor penetration in peripheral lung fields and excess deposition in large airways. Histogram analysis of images of the caudal portions of the lungs revealed nonuniform radionuclide deposition in horses with heaves and uniform radionuclide deposition in control horses. CONCLUSION: Administration of a single dose of aerosolized albuterol sulfate improved pulmonary distribution of aerosolized radiolabeled pentetate suspension in horses with heaves but did not alter pulmonary distribution in clinically normal horses. CLINICAL RELEVANCE: Precedent bronchodilator administration may improve pulmonary distribution of aerosolized, surface-active anti-inflammatory preparations.     

Inhalation of organic dusts and lipopolysaccharide increases gelatinolytic matrix metalloproteinases (MMPs) in the lungs of heaves horses

We report the effects of mouldy hay/straw exposure, inhaled hay dust suspension (HDS) and inhaled lipopolysaccharide (LPS) on bronchoalveolar lavage fluid (BALF) gelatinolytic matrix metalloproteinase (MMP) levels and degree of activation in healthy (n = 6) and heaves- (previously termed chronic obstructive pulmonary disease) affected (n = 6 or 7) horses. Gelatinolytic MMPs in BALF were quantified by zymography, and gelatinases were shown by Western immunoblotting to be MMP-2 and MMP-9. Hay/straw and HDS challenges increased BALF total gelatinolytic activity only in heaves horses, with the majority of gelatinolytic activity comprising pro- and active MMP-9. The 5 h duration hay/straw challenge increased BALF gelatinolytic MMP activity in heaves horses at 5 and 24 h after the start of this challenge, with activity returning to baseline by Day 4. In contrast to hay/straw and HDS challenges, LPS inhalation increased BALF gelatinolytic MMP activity in both groups. For all challenges, absolute BALF neutrophil counts were highly significantly correlated (P<0.0001) with levels of proMMP-9 and active MMP-9, but not with levels of MMP-2 (P>0.05). As gelatinolytic MMPs are pro-inflammatory agents, they may contribute to lung dysfunction and tissue destruction in heaves horses exposed to airborne organic stable dusts.     

Chronic exacerbation of equine heaves is associated with an increased expression of interleukin-17 mRNA in bronchoalveolar lavage cells

Recent finding suggests that T-cells may be involved in the pathogenesis of heaves in horses. However, little is known concerning their possible contribution to pulmonary neutrophilia, a characteristic finding in heaves. Interleukin (IL)-17 is a cytokine secreted by activated T-cells that indirectly promotes the maturation, chemotaxis and activation of neutrophils. We therefore hypothesized that IL-17 may be involved in the recruitment of neutrophils into the airways and that its mRNA expression would be increased in bronchoalveolar lavage (BAL) cells of horses with heaves. Heaves susceptible horses (n=4) and control horses (n=4) when in pasture (clinical remission) and after 35 days of continuous exposure to moldy hay were studied. BAL and respiratory mechanics measurements were performed at both time periods. The mRNA expression of IL-17 in BAL was studied using real-time polymerase chain reaction (PCR) and CD3-zeta was used as a marker of T-cell numbers. There was no significant difference in IL-17 mRNA expression between groups of horses while in pasture. However, stabling resulted in an increased expression of IL-17 in all horses with heaves but in none of the control horses. These preliminary results suggest that IL-17 may contribute in the pathogenesis of horses with heaves following chronic antigen challenge.     

IgG antibody responses to an inhaled antigen in horses with "heaves" (recurrent airway obstruction).

A controlled experimental system for the evaluation of pulmonary immune responses in horses with "heaves" (recurrent airway obstruction) has been developed. We hypothesized that the humoral immune response to an inhaled antigen in diseased horses would be different from that of healthy horses and that chronic pulmonary inflammation would bias the production of IgG isotypes in diseased horses as compared to healthy horses. Healthy and affected horses were housed in a natural challenge environment (stabled, fed dusty hay) and exposed by inhalation, to a nebulized solution of keyhole limpet hemocyanin (KLH). Sera and bronchoalveolar lavage fluids (BALFs) were collected from horses prior to and following their inhalation exposure to the antigen. Differential cell counts were performed on the cells in the BALF. An enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of IgGa, IgGb, IgG(T) and combined IgG specific for KLH in the sera and BALF. The percentages of neutrophils in the BALF of diseased horses were increased 4-6-fold over healthy horses. Combined IgG specific for KLH was significantly greater in BALF and serum from healthy compared to diseased horses. Differences in isotypes were also evident; however, only IgGb specific for KLH in the BALF was significantly increased in healthy versus diseased horses. Possible explanations for this difference include: (1) increased destruction of antigen before it could interact with lymphocytes, (2) down-regulation of IgGb production by inhibitory cytokines in diseased horses, or (3) binding of IgGb to Fc receptors on the large numbers of neutrophils in the lungs of diseased horses. In contrast to the prevailing notion that horses with heaves have exaggerated immune responses, our data suggest that diseased horses exposed to an aerosolized protein mount weaker IgG responses compared to healthy horses.     

骆驼风沙尘肺的研究

为探明风沙尘对动物健康的危害，对阿拉善右旗的７８例双峰驼的肺脏和肺门淋巴结进行了病理组织学观察和电子探针分析，同时也分析了风沙尘的矿物和元素组成。结果发现１７例驼骆的肺脏和肺门淋巴结有程度不同的尘肺病变，其中２例肺出现了典型的的结节。另有３９例双峰驼仅在淋巴结出现较严重的尘肺病变。肺和淋巴组织中的矿物主要为二氧化硅和铝硅酸盐化合物，与风沙尘的组成相同，从而证明风沙尘的长期吸入会引起骆驼的尘肺，其性质为一种铝硅酸盐尘肺。     

Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate

Work in humans and laboratory animals has identified a central role for cytokines and chemokines in development and persistence of lower airway inflammation. The objectives of this study were to determine interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha induction in bronchoalveolar lavage (BAL) of control horses and horses with heaves both during remission and exacerbation of the disease, and to determine the effect of therapy with inhaled fluticasone propionate on the cytokine profile of horses with heaves. IL-1 beta and TNF-alpha mRNA expression was significantly higher in horses with heaves after exposure to moldy hay compared to either values obtained during clinical remission or to healthy controls. IL-8 mRNA expression and protein concentrations were significantly higher in horses with heaves than in controls. Both IL-4 and IFN-gamma mRNA expression was increased at various times in heaves-susceptible horses compared to controls. IL-2, IL-5 and IL-10 mRNA expression was not detected in BAL cells of either group. Therapy with inhaled fluticasone propionate after induction of a severe heaves exacerbation resulted in complete resolution of clinical signs, normalization of pulmonary function tests, and significant decrease in BAL neutrophilia. This was associated with a significant decrease in IL-4 mRNA expression and increase in IFN-gamma/IL-4 ratio in horses with heaves. These results demonstrate the clinical efficacy of inhaled fluticasone propionate for the treatment of heaves and suggest a role for cytokines in the development of lower airway inflammation in heaves-susceptible horses.     

Ultrastructural findings in horses with chronic obstructive pulmonary disease (COPD). I: Alterations of the larger conducting airways

Extensive light and electron microscope studies of the conducting airways were carried out in 28 horses with varying degrees of clinically manifested chronic obstructive pulmonary disease (COPD) and in 8 horses with normal lungs. The principal ultrastructural changes were found in the ciliated cells. There was focal loss of ciliated cells, which were replaced by undifferentiated cells in a largely hyperplastic epithelium, and some horses, independent of the degree of severity of the disease, showed various types of ciliary malformation. The finding of dilated intercellular clefts and accumulations of mast cells was interpreted as morphological evidence of non-specific mucosal hyperreactivity. Interstitial cells with intracytoplasmal crystal inclusions, the cause of which is not clear, were seen in many horses. Comparison between the clinical diagnosis and the morphological findings showed partial correlation. The ciliary loss, the appearance of peribronchial inflammatory processes and the occurrence of intracytoplasmic crystalline inclusions showed a positive correlation. In 12 of 28 cases, the severity of clinical diagnosis agreed with the degree of the morphological findings. The changes in the conducting airways were interpreted pathogenetically as reactive processes to changes in the small airways in the course of equine COPD.