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

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.

间质性肺疾病涉及一组预后不良的疾病，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。在肺泡间质损伤的肺组织中，使肺泡上皮细胞再生对于损伤肺的修复非常重要。最近的多项研究表明，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。本研究的目的是阐明血管紧张素 II 受体 1 (AT1) 导致间质性肺损伤和纤维化的机制，并评估 AT1 选择性拮抗剂（坎地沙坦）作为治疗剂对抗博莱霉素诱导的大鼠肺损伤的疗效。正常肺中 AT1 受体的表达分布对于许多类型的细胞（包括肺泡巨噬细胞和 II 型肺细胞）来说是非特异性的。它们在受损肺部的中性粒细胞、肺泡巨噬细胞和成纤维细胞中的表达比其他类型的细胞更广泛。给予坎地沙坦可显着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细胞数量的增加，但不会抑制 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。 AT1 拮抗剂的推测机制是基于防止 II 型肺细胞凋亡。

项目成果

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