BackgroundPyroptosis and polarization are significant contributors to the onset and development of many diseases. At present, the relationship between pyroptosis and polarization in acute lung injury (ALI) caused by sepsis remains unclear.MethodsThe ALI model for sepsis was created in mice and categorized into the blank control, lipopolysaccharide (LPS) group, LPS + low‐dose Belnacasan group, LPS + high‐dose Belnacasan group, LPS + low‐dose Wedelolactone group, LPS + high‐dose Wedelolactone group, and positive control group. The wet‐dry specific gravity was evaluated to compare pulmonary edema. Hematoxylin–eosin, Masson, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining techniques were conducted to observe and contrast the pathological changes in lung tissue. ELISA was utilized to identify M1 and M2 macrophages and correlated inflammatory factors. Immunohistochemical staining and flow cytometry were employed to identify markers of M1 and M2 macrophages in lung tissue. Propidium iodide staining, together with flow cytometry, was utilized to observe the degree and positive rate of pyroptosis of alveolar macrophages. Western blot analysis was conducted to detect the expression levels of Caspase 1, Caspase 11, GSDMD, and IL‐18 in the lung tissues of each group. The real‐time quantitative polymerase chain reaction method was used to ascertain relative expression levels of NLRP3, Caspase 1, Caspase 11, GSDMD, IL‐18, iNOS, and Arg‐1 in lung tissues of all groups.ResultsIn mice with sepsis‐induced ALI, both classical and nonclassical pathways of pyroptosis are observed. Inhibiting pyroptosis has been found to ameliorate lung injury, pulmonary edema, and inflammation induced by LPS. Notably, the expression of NLRP3, Caspase 1, Caspase 11, GSDMD, IL‐1β, IL‐18, TGF‐β, CD86, CD206, iNOS, and Arg‐1 were all altered in this process. Additionally, alveolar macrophages were polarized along with pyroptosis in mice with ALI caused by sepsis.ConclusionPyroptosis of alveolar macrophages in the context of ALI in mice infected with sepsis has been linked to the polarization of alveolar macrophages toward type M1.

中文翻译：

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脂多糖致小鼠脓毒症急性肺损伤中巨噬细胞的焦亡和极化

背景焦亡和极化是许多疾病发生和发展的重要因素。目前，脓毒症引起的急性肺损伤（ALI）中焦亡与极化的关系尚不清楚。方法建立脓毒症小鼠ALI模型，分为空白对照组、脂多糖（LPS）组、LPS+小剂量Belnacasan组、LPS+高剂量Belnacasan组、LPS+低剂量蜈蚣内酯组、LPS+高剂量蜈蚣内酯组、阳性对照组。评估干湿比重以比较肺水肿。采用苏木精-伊红、Masson、末端脱氧核苷酸转移酶dUTP缺口末端标记染色技术观察和对比肺组织病理变化。利用 ELISA 鉴定 M1 和 M2 巨噬细胞以及相关炎症因子。采用免疫组织化学染色和流式细胞术来鉴定肺组织中M1和M2巨噬细胞的标记物。碘化丙啶染色结合流式细胞术观察肺泡巨噬细胞焦亡程度及阳性率。 Western blot分析检测各组肺组织中Caspase 1、Caspase 11、GSDMD、IL-18的表达量。采用实时定量聚合酶链反应法测定各组小鼠肺组织中NLRP3、Caspase 1、Caspase 11、GSDMD、IL-18、iNOS、Arg-1的相对表达水平。 ALI、焦亡的经典和非经典途径均被观察到。研究发现，抑制焦亡可以改善 LPS 引起的肺损伤、肺水肿和炎症。值得注意的是，NLRP3、Caspase 1、Caspase 11、GSDMD、IL-1β、IL-18、TGF-β、CD86、CD206、iNOS 和 Arg-1 的表达在此过程中均发生改变。此外，在脓毒症引起的ALI小鼠中，肺泡巨噬细胞随着细胞焦亡而极化。结论感染脓毒症的小鼠在ALI的情况下，肺泡巨噬细胞的焦亡与肺泡巨噬细胞向M1型的极化有关。