Type II pneumocytes as a protective factor against interstitial lung injury

间质性肺疾病指预后不良的一组，包括特发性肺纤维化(IPF)。肺纤维化是一种常见的病理生理改变，在肺泡间质损伤的肺组织中，使肺泡上皮细胞再生对损伤肺的修复非常重要。最近的一些研究表明，肾素-血管紧张素系统诱导肺纤维化，而II型肺泡细胞的凋亡是其机制中的一个关键因素。然而，这一系统的确切方式尚不清楚。本研究旨在阐明血管紧张素II受体1(AT1)介导的间质性肺损伤及其继发纤维化的机制，并评价AT1选择性拮抗剂坎地沙坦对博莱霉素性肺损伤的治疗作用。AT1受体在正常肺组织中的表达在肺泡巨噬细胞和II型肺泡细胞等多种细胞中的分布是非特异性的。在受损肺中，它们在中性粒细胞、肺泡巨噬细胞和成纤维细胞中的表达比在其他类型的细胞中更广泛。给予坎地沙坦显著抑制作为纤维化定量指标的羟脯氨酸含量的增加，以及中性粒细胞和肺泡巨噬细胞数量的增加，而不抑制AT1的表达增加。因此，这种AT1拮抗剂可能提供一种调节肺纤维化过程的能力。AT1拮抗剂的一种推测机制是基于阻止II型肺泡细胞的凋亡。

Interstitial lung diseases involve a group showing poor prognosis including idiopathic pulmonary fibrosis (IPF). A common pathophysiological change is irreversible fibrosis.In lung tissues injured in alveolar interstitum, to make alveolar epithelial cells regenerate is very important for repair of the injured lung. Several recent studies showed that rennin-angiotensin system induces lung fibrosis and that apoptosis of type II pneumocytes is a key factor of its mechanism. However, precise manner of this system is unknown. Aims of this study were to clarify a mechanism of interstital lung injury and following fibrosis via angiotensin II receptor 1 (AT1) and to estimate an efficacy of AT1 selective antagonist (Candesartan) as a therapeutic agent against bleomycin-induced lung injury prepared in rats. Distribution of expression of AT1 receptors in normal lungs was nonspecific for many types of cells including alveolar macrophages and type II pneumocytes. Their expression in injured lungs was more extensive in neutrophils, alveolar macrophages and fibroblasts than in other types of cells. Administration of Candesartan significantly inhibited an increased content of hydroxyproline as a quantitative indicator of fibrosis, and an increased cell number of neutrophils and alveolar macrophages, whereas it did not inhibit an increased expression of AT1. Thus, this AT1 antagonist may provide an ability to modulate a process of fibrosis in the lung. A speculated mechanism by the AT1 antagonist is based on prevention of apoptosis of type II pneumocytes.