Lakatos Heather F, Burgess Heather A, Thatcher Thomas H, Redonnet Michelle R, Hernady Eric, Williams Jacqueline P, Sime Patricia J
Department of Environmental Medicine and Lung Biology and Disease Program, University of Rochester, Rochester, New York 14642, USA.
Exp Lung Res. 2006 May;32(5):181-99. doi: 10.1080/01902140600817465.
Instillation of crystalline silica into the lungs of mice is a common experimental model of pulmonary fibrosis. Typically, a suspension of silica in saline is injected into the trachea via intubation or surgical tracheostomy. These techniques require a high degree of technical skill, have a lengthy training period, and can suffer from a high failure rate. In oropharyngeal aspiration, a droplet of liquid is placed in the animal's mouth while simultaneously holding its tongue (to block the swallow reflex) and pinching its nose shut, forcing it to breathe through its mouth, aspirating the liquid. To determine whether oropharyngeal aspiration (OA) could replace intratracheal instillation (IT) in a model of silica-induced fibrosis, a comparison was performed. Crystalline silica was introduced into the lungs of male C57BL/6 mice by the IT or OA procedure, and the resulting inflammation and fibrosis was assessed after 3 weeks. IT and OA instillation of silica both resulted in neutrophilic inflammation and fibrotic changes, including interstitial fibrosis and dense fibrotic foci. Mice treated via IT demonstrated a few large lesions proximal to conducting airways with little involvement of the distal parenchyma and large interanimal variability. In contrast, OA resulted in a diffuse pathology with numerous fibrotic foci distributed throughout the lung parenchyma, which is more representative of human fibrotic lung disease. OA- but not IT-treated mice exhibited significantly increased lung collagen content. Furthermore, the interanimal variability within the OA group was significantly less than in the IT group. Oropharyngeal aspiration should be considered as an alternative to intratracheal instillation of silica and other particulates in studies of respiratory toxicity and lung disease.
将结晶二氧化硅注入小鼠肺部是肺纤维化常见的实验模型。通常，通过插管或手术气管切开术将二氧化硅盐水悬浮液注入气管。这些技术需要高度的技术技能，培训期长，且失败率高。在口咽吸入法中，将一滴液体置于动物口中，同时捏住其舌头（以阻断吞咽反射）并捏住其鼻子使其闭嘴，迫使其通过口腔呼吸，从而吸入液体。为了确定在二氧化硅诱导的纤维化模型中口咽吸入法（OA）是否可以替代气管内注入法（IT），进行了一项比较。通过IT或OA程序将结晶二氧化硅引入雄性C57BL/6小鼠的肺部，并在3周后评估由此产生的炎症和纤维化。二氧化硅的IT和OA注入均导致中性粒细胞炎症和纤维化变化，包括间质纤维化和致密的纤维化灶。通过IT治疗的小鼠在传导气道近端出现一些大的病变，远端实质受累较少，且动物间差异较大。相比之下，OA导致弥漫性病变，肺实质内分布着许多纤维化灶，这更能代表人类纤维化肺病。OA处理而非IT处理的小鼠肺胶原蛋白含量显著增加。此外，OA组内动物间的变异性明显小于IT组。在呼吸毒性和肺病研究中，口咽吸入法应被视为气管内注入二氧化硅和其他颗粒的替代方法。
