目的探讨Parkin过表达诱导的线粒体自噬对缓解劳力性中暑（EHS）大鼠急性肺损伤的作用。将80只SD大鼠分为4组：对照组（CON组）、Parkin过表达对照组（CON  Parkin组）、劳力性中暑组（EHS组）、劳力性中暑Parkin过表达组（EHS  Parkin组）。将携带 Parkin 基因的腺相关病毒静脉注射到大鼠体内，使肺组织中 Parkin 过度表达。建立劳力性中暑大鼠模型，绘制生存曲线。进行肺显微CT，测量肺系数和肺微血管通透性。采用酶联免疫吸附法（ELISA）测定白细胞介素6（IL-6）、白细胞介素1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、活性氧（ROS）水平。 ）。采用透射电镜观察肺组织II型上皮细胞线粒体形态。使用免疫荧光测定肺组织的凋亡、线粒体自噬水平以及 Pink1 和 Parkin 的共定位。 Western blot检测大鼠肺组织中Pink1、Parkin、MFN2、PTEN-L、PTEN、p62、微管相关蛋白1轻链3（LC3）的表达情况。与CON组相比，肺损伤更严重EHS大鼠中IL-6、IL-1β、TNF-α水平更高。 EHS大鼠肺组织中LC3-II/LC3-I比值以及LC3和Tom20的共定位均降低。与EHS组相比，EHS  Parkin过表达组大鼠存活率显着升高，肺系数和肺微血管通透性降低，渗出、实变等病理改变明显减轻。 IL-6、IL-1β、TNF-α、ROS水平显着降低； II型肺泡上皮细胞线粒体肿胀程度减轻，未观察到空泡化。肺组织凋亡减少，Pink1和Parkin以及LC3和Tom20的共定位荧光增加。肺组织中Parkin表达及LC3-II/LC3-I比值均升高，而P62、Pink1、MFN2、PTEN-L表达降低。Pink1/Parkin介导的线粒体自噬功能障碍是其机制之一EHS 大鼠急性肺损伤，激活 Parkin 过表达诱导的线粒体自噬可以减轻 EHS 引起的急性肺损伤。© 2024。作者。

To investigate the role of Parkin overexpression-induecd mitophagy in alleviating acute lung injury of exertional heat stroke(EHS) rats.Eighty SD rats were divided into four groups: Control group (CON group), Control Parkin overexpression group (CON + Parkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHS + Parkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung Micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. Enzyme-linked immunosorbent assays(ELISA) were used to determine the levels of interleukin-6(IL-6), interleukin-1β(IL-1β), Tumor necrosis factor-α(TNF-α), and reactive oxygen species(ROS). The morphology of mitochondria in type II epithelial cells of lung tissue was observed using transmission electron microscopy. The apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, MFN2, PTEN-L, PTEN, p62, and microtubule associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by western blot.Compared with the CON group, there were more severe lung injury and more higher levels of IL-6, IL-1β, TNF-α in EHS rats. Both of the LC3-II/LC3-I ratio and the co-localization of LC3 and Tom20 in the lung tissue of EHS rats decreased. Compared with the EHS group, the survival rate of rats in the EHS + Parkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly alleviated. The levels of IL-6, IL-1β, TNF-α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased.Pink1/Parkin-mediated mitophagy dysfunction is one of the mechanisms underlying acute lung injury in rats with EHS, and activation of Parkin overexpression induced-mitophagy can alleviate acute lung injury caused by EHS.© 2024. The Author(s).