哮喘豚鼠模型细支气管和肺组织的病理学研究

目的深化对哮喘小气道及肺组织病理改变的认识。方法以卵蛋白致敏法制备哮喘豚鼠模型，共设6组对照组、哮喘1日组、哮喘4日组、哮喘14日组、氟美松组及布地奈德组。观察和比较6组豚鼠大、小气道及肺泡区病理学改变及炎性细胞浸润情况。行支气管肺泡灌洗，并行细胞计数及分类。电镜观察肺泡细胞的形态。测定支气管肺泡灌洗液(BALF)中总磷脂的含量。结果各哮喘模型组豚鼠支气管黏膜上皮、基底膜、平滑肌增厚，肺泡隔较对照组显著增宽(P<0.001)，肺泡腔变小;大、小气道及肺泡区有大量嗜酸粒细胞及淋巴细胞浸润；BALF中细胞总数较对照组显著增多(P<0.01)，早期以中性粒细胞为主，晚期则以嗜酸粒细胞和淋巴细胞为主；电镜示肺泡Ⅱ型上皮细胞肿胀、板层体排空及部分脱落;BALF中总磷脂含量较对照组显著降低(P<0.01)。氟美松组及布地奈德组以上改变显著减轻,接近对照组。结论支气管哮喘时细支气管和肺组织也广泛存在着以嗜酸粒细胞为主的炎症;肺泡细胞在形态学改变的同时，也发生着功能的改变。

A pathologic study on the bronchioles and lung tissues in guinea pig asthma models

OBJECTIVE: To probe further the pathologic changes in peripheral airways and lung tissues and to observe the changes of surfactant in asthma. METHODS: (1) The guinea pig asthma models were established with ovalbumin challenge method. (2) 6 groups were studied: control group, asthma group of day 1, asthma group of day 4, asthma group of day 14, intraperitoneal dexamethasone group, and budesonide inhalation group. (3) The pathologic changes were observed under optical and electron microscope. (4) The total and differential white blood cells counts of bronchoalveolar lavage fluid(BALF) were carried out. (5) The total amounts of phospholipids which represent the levels of pulmonary surfactant were measured with phosphorus detection method. RESULTS: (1) Significant hyperplasia of mucous membrane, basement membrane, and smooth muscle layer of central and peripheral airways in the asthma groups were seen. The alveolar walls were significantly thickened and alveolar spaces diminished (P < 0.001, compared with the control group). Significant infiltration of eosinophils and lymphocytes were observed in airways and lung tissues. (2) The total cell number and the number eosinophils and lymphocytes in BALF were significantly increased in the asthma groups than those in the control group(P < 0.01). Neutrophils were dominant at early stage, but eosinophils and lymphocytes at late stage. (3) The ultrastructural changes of type II alveolar cells in asthma group included cell swelling, evacuation of lamellar bodies and partial cell desquamation. (4) The total amount of phospholipids in BALF was significantly decreased in the asthma groups as compared with that in the control group (P < 0.01). The above changes were significantly improved in both corticosteroid treated groups. CONCLUSION: Widespread and significant inflammation with eosinophilic infiltration exists in the bronchioles and alveolar walls in guinea pig asthma models. Not only there is structural change, but also the function of alveolar cells is influenced. Asthma is a disease involving the whole airway and lung system.