Background and Purpose. Stroke-associated pneumonia (SAP) is a common complication after stroke that increases the mortality of patients. Although there have been many studies suggesting that stroke can increase patient susceptibility to pneumonia, it is still unknown whether the treatment of stroke can also improve lung injury. We used NLRP3-knockout (NLRP3-KO) mice to verify that an improvement in brain injury would also be beneficial to lung injury and further confirm the relationship between stroke and pneumonia. Methods. C57/BL6 wild-type (WT) and NLRP3-KO mice were used to construct middle cerebral artery occlusion (MCAO) models. 2,3,5-Triphenyltetrazolium chloride (TTC) was used to evaluate brain damage, and neurological deficits were assessed. Then, lung tissue injury was examined in the different groups of mice by hematoxylin-eosin (HE) staining. Inflammation (macrophage and neutrophil infiltration, NLRP3-associated inflammatory molecules) and oxidative stress (reactive oxygen species, ROS) in the lungs were comprehensively examined by immunofluorescence staining and Western blotting. Results. First, our findings demonstrated that NLRP3 knockout had a protective effect against cerebral ischemia–reperfusion injury after MCAO. Second, by reducing brain damage after MCAO, lung inflammation was also alleviated. Immunofluorescence staining showed that NLRP3-KO-MCAO mice had reduced inflammatory effector molecule (caspase-1 and IL-1β) expression and macrophage and neutrophil infiltration in the lung, as well as remissive oxidative stress state in the lung, compared with WT-MCAO mice. We also observed a decrease in phosphorylated p65 (p-p65) (an NF-κB factor) in NLRP3-KO-MCAO mice, suggesting that the NF-κB pathway was involved in the protective effect of NLRP3 gene knockout on stroke-induced lung injury. Conclusions. NLRP3 inflammasome knockout not only is beneficial for cerebral ischemia–reperfusion injury but also reduces the severity of poststroke lung injury by reducing brain damage. It has been confirmed that there is a relationship between central insult and peripheral organ injury, and protecting the brain can prevent peripheral organ damage.

中文翻译：

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NLRP3 敲除可防止脑缺血再灌注引起的肺损伤

背景和目的。中风相关性肺炎 (SAP) 是中风后常见的并发症，会增加患者的死亡率。尽管已有多项研究表明中风会增加患者对肺炎的易感性，但中风的治疗是否也能改善肺损伤尚不清楚。我们使用 NLRP3 敲除 (NLRP3-KO) 小鼠来验证脑损伤的改善也将有益于肺损伤，并进一步证实中风和肺炎之间的关系。方法. C57/BL6 野生型 (WT) 和 NLRP3-KO 小鼠用于构建大脑中动脉闭塞 (MCAO) 模型。2,3,5-氯化三苯基四唑 (TTC) 用于评估脑损伤，并评估神经功能缺损。然后，通过苏木精 - 伊红（HE）染色检查不同组小鼠的肺组织损伤。通过免疫荧光染色和蛋白质印迹全面检查肺部炎症（巨噬细胞和中性粒细胞浸润，NLRP3 相关炎症分子）和氧化应激（活性氧，ROS）。结果. 首先，我们的研究结果表明，NLRP3 敲除对 MCAO 后的脑缺血再灌注损伤具有保护作用。其次，通过减少 MCAO 后的脑损伤，肺部炎症也得到了缓解。免疫荧光染色显示，与 WT-相比，NLRP3-KO-MCAO 小鼠的肺中炎症效应分子（caspase-1 和 IL-1 β）表达、巨噬细胞和中性粒细胞浸润以及肺中缓解性氧化应激状态降低。 MCAO 小鼠。我们还观察到 NLRP3-KO-MCAO 小鼠的磷酸化 p65 (p-p65)（一种 NF-κB因子）减少，这表明 NF-κB通路参与了 NLRP3 基因敲除对卒中的保护作用。诱发肺损伤。结论. NLRP3 炎性体敲除不仅有利于脑缺血再灌注损伤，而且通过减少脑损伤来降低中风后肺损伤的严重程度。已证实中枢损伤与外周器官损伤存在关系，保护大脑可预防外周器官损伤。