Kenyon N J, Ward R W, McGrew G, Last J A
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of California-Davis, Davis, CA 95616, USA.
Thorax. 2003 Sep;58(9):772-7. doi: 10.1136/thorax.58.9.772.
Subepithelial collagen and extracellular matrix protein deposition are important pathophysiological components of airway remodelling in chronic asthma. Animal models based on the local reaction to antigens show structural alterations in the airway submucosal region and provide important information regarding disease pathophysiology. We describe a murine model of peribronchial fibrosis using intratracheally instilled transforming growth factor (TGF)-beta(1) in BALB/C mice that facilitates a mechanistic approach to understanding the cellular and molecular pathways leading to airway fibrosis.
BALB/C mice were intratracheally instilled with either TGF-beta(1) or buffered saline. Airway fibrosis was assessed by light microscopy, hydroxyproline content, and polymerase chain reaction (PCR) for collagen I and III on microdissected airway samples. The lysyl oxidase inhibitor beta-aminoproprionitrile (BAPN) was administered to TGF-beta(1) treated mice to block airway collagen deposition. Airway hyperresponsiveness was also measured after treatment with TGF-beta(1).
During the 7 days after administration of TGF-beta(1) the mice developed increased subepithelial collagen which could be blocked by BAPN. Increased mRNAs for collagen types I and III were seen in microdissected airways 1 week after TGF-beta(1), and significantly increased total collagen was found in the airways 4 weeks after TGF-beta(1). A detectable increase in airway hyperreactivity occurred.
This new model should facilitate detailed study of airway remodelling that occurs in the absence of detectable cellular inflammation, and allow examination of the functional consequences of a major structural alteration in the conducting airways uncomplicated by inflammatory cell influx.
上皮下胶原蛋白和细胞外基质蛋白沉积是慢性哮喘气道重塑的重要病理生理组成部分。基于对抗原局部反应的动物模型显示气道黏膜下区域存在结构改变，并提供了有关疾病病理生理学的重要信息。我们描述了一种在BALB/C小鼠中通过气管内注入转化生长因子（TGF）-β1建立的支气管周围纤维化小鼠模型，该模型有助于从机制上理解导致气道纤维化的细胞和分子途径。
将TGF-β1或缓冲盐水经气管内注入BALB/C小鼠。通过光学显微镜、羟脯氨酸含量以及对显微切割的气道样本进行I型和III型胶原蛋白的聚合酶链反应（PCR）来评估气道纤维化。向经TGF-β1处理的小鼠施用赖氨酰氧化酶抑制剂β-氨基丙腈（BAPN）以阻断气道胶原蛋白沉积。在用TGF-β1处理后还测量了气道高反应性。
在给予TGF-β1后的7天内，小鼠上皮下胶原蛋白增加，这可被BAPN阻断。在给予TGF-β1后1周，显微切割的气道中可见I型和III型胶原蛋白的mRNA增加，在给予TGF-β1后4周，气道中总胶原蛋白显著增加。出现了可检测到的气道高反应性增加。
这个新模型应有助于详细研究在无明显细胞炎症情况下发生的气道重塑，并允许检查在无炎症细胞流入情况下传导气道主要结构改变的功能后果。
