Type II pneumocytes as a protective factor against interstitial lung injury

间质性肺疾病包括特发性肺纤维化（IPF）等预后不良的疾病。不可逆纤维化是一种常见的病理生理变化。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。近年来多项研究表明肾素-血管紧张素系统诱导肺纤维化，II型肺细胞凋亡是其机制的关键因素。然而，该系统的精确方式尚不清楚。本研究的目的是通过血管紧张素II受体1 （AT1）阐明肺间质损伤和纤维化的机制，并评估AT1选择性拮抗剂（坎地沙坦）作为治疗大鼠博莱霉素诱导的肺损伤的疗效。AT1受体在正常肺中的表达分布对包括肺泡巨噬细胞和II型肺细胞在内的许多类型的细胞都是非特异性的。它们在损伤肺中的表达在中性粒细胞、肺泡巨噬细胞和成纤维细胞中比在其他类型的细胞中更广泛。坎地沙坦显著抑制羟脯氨酸（纤维化定量指标）含量的增加，中性粒细胞和肺泡巨噬细胞数量的增加，而不抑制AT1表达的增加。因此，这种AT1拮抗剂可能具有调节肺纤维化过程的能力。推测AT1拮抗剂的作用机制是基于防止II型肺细胞凋亡。

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.