Type II pneumocytes as a protective factor against interstitial lung injury

II型肺细胞作为间质性肺损伤的保护因子

• 批准号: 13670609
• 负责人: TAKAHASHI Hiroki
• 金额: $ 1.79万
• 依托单位: Sapporo Medical University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670609/
• 关键词: angiotensin receptor 1; Candesartan; interstitial lung injury; lung fibrosis; type II pneumocytes; alveolar macrophage; neutrophil; 肺線維化; Renin-Angiotensin系; Angiotensin II receptor 1; candesartan; 肺胞II型上皮細胞; 急性肺傷害; 線維化; アンギオテンシンII; ブレオマイシン; angiotensin receptor 1; Candesartan; interstitial lung injury; lung fibrosis; type II pneumocytes; alveolar macrophage; neutrophil; 肺線維化; Renin-Angiotensin系; Angiotensin II receptor 1; candesartan; 肺胞II型上皮細胞; 急性肺傷害; 線維化; アンギオテンシンII; ブレオマイシン

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.

间质性肺部疾病涉及一组显示不良预后的组，包括特发性肺纤维化（IPF）。常见的病理生理变化是不可逆的纤维化。最近的几项研究表明，肾素 - 血管紧张素系统诱导肺纤维化，II型肺细胞的凋亡是其机制的关键因素。但是，该系统的精确方式尚不清楚。这项研究的目的是阐明通过血管紧张素II受体1（AT1）纤维化的机制，并估计AT1选择性拮抗剂（Candesartan）作为针对白霉素诱导的大鼠肺损伤的治疗剂的疗效。对于包括肺泡巨噬细胞和II型肺细胞在内的许多类型的细胞，正常肺中AT1受体的表达分布是非特异性的。与其他类型的细胞相比，它们在受伤的肺中的表达在中性粒细胞，肺泡巨噬细胞和成纤维细胞中更为广泛。坎迪萨尔人的给药显着抑制了羟丙烯的含量增加，作为纤维化的定量指标，中性粒细胞和肺泡巨噬细胞的细胞数量增加，而它并未抑制AT1的表达增加。因此，该AT1拮抗剂可以提供调节肺纤维化过程的能力。 AT1拮抗剂的推测机制基于预防II型肺细胞凋亡。