Autophagy has been implicated in the pathogenesis of various lung diseases. This study aimed to investigate the role of autophagy in lung injury induced by high-altitude hypoxia. Wistar rats were randomized into four groups for exposure to normal altitude or high altitude for 1, 7, 14 and 21 days with no treatment or with the treatment of 1 mg/kg rapamycin or 2 mg/kg 3-methyladenine (3-MA) for consecutive 21 days respectively. In control rats, the alveolar structure was intact with regularly arranged cells. However, inflammatory cell infiltration and shrunk alveoli were observed in rats exposed to hypoxia. Rapamycin treatment led to many shrunken alveoli with a large number of red blood cells in them. In contrast, 3-MA treatment led to almost intact alveoli or only a few shrunken alveoli. Compared to the control group exposure to high-altitude hypoxia for longer periods resulted in the aggravation of the lung injury, the formation of autophagosomes with a double-membrane structure and increased levels of Beclin-1 and LC3-II in alveolar tissues. Rapamycin treatment resulted in significant increase in Beclin-1 and LC3-II levels and further aggravation of alveolar tissue damage, while 3-MA treatment led to opposite effects. In conclusion, exposure to high-altitude hypoxia can induce autophagy of alveolar cells, which may be an important mechanism of high-altitude hypoxia-induced lung injury. The inhibition of autophagy may be a promising therapy strategy for high-altitude hypoxia-induced lung injury.

中文翻译：

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高原缺氧增加自噬导致大鼠肺泡细胞损伤

自噬与多种肺部疾病的发病机制有关。本研究旨在探讨自噬在高原缺氧所致肺损伤中的作用。Wistar 大鼠被随机分为四组，分别暴露于正常海拔或高海拔地区 1、7、14 和 21 天，不治疗或接受 1 mg/kg 雷帕霉素或 2 mg/kg 3-甲基腺嘌呤 (3-MA) 治疗分别连续21天。在对照大鼠中，肺泡结构完整，细胞排列规则。然而，在缺氧的大鼠中观察到炎症细胞浸润和肺泡收缩。雷帕霉素治疗导致许多肺泡萎缩，其中含有大量红细胞。相比之下，3-MA 治疗导致肺泡几乎完整或仅有少数肺泡萎缩。与对照组相比，较长时间的高原缺氧导致肺损伤加重，双膜结构自噬体形成，肺泡组织中Beclin-1和LC3-II水平升高。雷帕霉素治疗导致Beclin-1和LC3-II水平显着升高，进一步加重肺泡组织损伤，而3-MA治疗则产生相反的效果。综上所述，高原缺氧可诱导肺泡细胞自噬，这可能是高原缺氧所致肺损伤的重要机制。抑制自噬可能是治疗高原缺氧性肺损伤的一种有前途的治疗策略。