Chung-Ming Chen, Yaw-Dong Lang, Hsiu-Chu Chou, Leng-Fang WangYaw-Dong Lang, Hsiu-Chu Chou, Leng-Fang WangChung-Ming Chen2026-05-192026-05-192010https://203.71.86.71/handle/123456789/14859Objectives: Oxygen toxicity plays an important role in the lung injury that may lead to lung fibrosis. Angiotensin II is a profibrotic mediator which induces human lung fibroblast proliferation. We investigated the effects of hyperoxia on the components of renin-angiotensin system (RAS) and collagen production and the therapeutic effect of angiotensin II type 1 receptor (AT1R) blocker in room air- and hyperoxia-exposed newborn rats. Methods: Rat pups were exposed to 1 week of > 95% O2 and a further 2 weeks of 60% O2. AT1R blocker treated-rats received intraperitoneal injection of losartan 10 mg/kg/day during the first postnatal week and 5 mg/kg/day from postnatal 2-week to 3-week old. Main Results: Hyperoxia significantly increased total collagen, type I collagen, and α-smooth muscle actin (α-SMA) expression when compared to room air-exposed rats on postnatal days 7 and 21. RAS components including angiotensinogen, angiotensin-converting enzyme, angiotensin II, and AT1R were significantly increased by hyperoxia whereas AT2R was not significantly different when compared to room air-exposed rats on postnatal days 7 and 21. Hyperoxia significantly increased extracelluar signal-regulated kinase phosphorylation but did not affect the phosphorylation levels of p38 or c-Jun N-terminal kinase on postnatal days 7 and 21. Losartan significantly reduced total collagen and type I collagen and α-SMA expression when compared to room air-exposed rats on postnatal days 7 and 21. Conclusion: Hyperoxia induces lung collagen production via the activation of RAS in newborn rats and losartan reduces lung collagen production. AT1R blocker may represent a novel therapeutic strategy for hyperoxia-induced lung fibrosis.32256 bytesapplication/msworden-US小兒學科conference