Wang Xiaoxia, Xu Tianxiang, Jin Jiajia, Ting Gao M M, Wan Bing, Gong Mei, Bai Lingxiao, Lv Tangfeng, Song Yong
Intensive Care Unit, Inner Mongolia People's Hospital Hohhot Inner Mongolia Autonomous Region China.
Center of Tumor, Inner Mongolia People's Hospital Hohhot Inner Mongolia Autonomous Region China.
Pulm Circ. 2022 Apr 20;12(2):e12070. doi: 10.1002/pul2.12070. eCollection 2022 Apr.
This study aims to determine the function of topotecan (TPT) in acute lung injury (ALI) induced by sepsis. The mouse sepsis model was constructed through cecal ligation and puncture (CLP). The ALI score and lung wet/dry (W/D) weight ratio were applied to evaluate the level of lung injury. Hematoxylin-eosin staining was used to examine the role of TPT in lung tissue in a CLP-induced ALI mouse model. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were used to detect the concentrations of inflammatory factors, such as interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α. Western blot was used to detect relevant protein levels in the nuclear factor-κB (NF-κB) pathway. Moreover, 10-day survival was recorded by constructing the CLP model. The results indicated that TPT could improve lung tissue damage in mice and could significantly reduce lung injury scores ( < 0.01) and the W/D ratio ( < 0.05). Treatment with ammonium pyrrolidinedithiocarbamate obtained the similar results with the TPT treatment. Both significantly reduced the inflammatory response in the lungs, including reducing the number of neutrophils and total cells in the bronchoalveolar lavage fluid (BALF), significantly reducing the total protein concentration of the BALF, and significantly inhibiting the activity of MPO. Both also inhibited inflammatory cytokine expression and the levels of NF-κB pathway proteins induced by sepsis. Furthermore, TPT significantly improved survival in sepsis. TPT improves ALI in the CLP model by inhibiting the NF-κB pathway, preventing fatal inflammation.
本研究旨在确定拓扑替康（TPT）在脓毒症诱导的急性肺损伤（ALI）中的作用。通过盲肠结扎和穿刺（CLP）构建小鼠脓毒症模型。应用ALI评分和肺湿/干（W/D）重量比来评估肺损伤程度。苏木精-伊红染色用于检测TPT在CLP诱导的ALI小鼠模型肺组织中的作用。酶联免疫吸附测定和定量实时聚合酶链反应用于检测炎症因子如白细胞介素-6（IL-6）、IL-1β和肿瘤坏死因子-α的浓度。蛋白质免疫印迹法用于检测核因子-κB（NF-κB）通路中的相关蛋白水平。此外，通过构建CLP模型记录10天生存率。结果表明，TPT可改善小鼠肺组织损伤，并可显著降低肺损伤评分（<0.01）和W/D比值（<0.05）。用吡咯烷二硫代氨基甲酸铵治疗获得了与TPT治疗相似的结果。两者均显著降低肺部炎症反应，包括减少支气管肺泡灌洗液（BALF）中的中性粒细胞和总细胞数量，显著降低BALF的总蛋白浓度，并显著抑制MPO活性。两者还抑制炎症细胞因子表达和脓毒症诱导的NF-κB通路蛋白水平。此外，TPT显著提高脓毒症的生存率。TPT通过抑制NF-κB通路改善CLP模型中的ALI，预防致命性炎症。
