茯苓酸通过Keap1-Nrf2/HO-1途径抑制铁死亡缓解脂多糖诱导的肺损伤  

Pachymic acid inhabiting ferroptosis through Keap1-Nrf2/HO-1 pathway to alleviate LPS-induced acute lung injury

作　　者：李昭伦 孙文静[1] 刘晓明 张殿普 桑义 许从磊 李晓梅[1] LI Zhaolun;SUN Wenjing;LIU Xiaoming;ZHANG Dianpu;SANG Yi;XU Conglei;LI Xiaomei(Department of Pediatric Intensive Care,Affiliated Hospital of Binzhou Medical College,Binzhou,Shandong 256600,China)

机构地区：[1]滨州医学院附属医院儿童重症医学科,山东滨州256600

出　　处：《临床肺科杂志》2024年第6期888-893,900,共7页Journal of Clinical Pulmonary Medicine

基　　金：滨州医学院“临床+X”项目(No.BY2021LCX29)。

摘　　要：目的 探究茯苓酸(PA)对脂多糖(LPS)诱导的大鼠和支气管上皮BEAS-2B细胞的急性肺损伤(ALI)的作用及机制。方法 通过LPS诱导幼年Sprague-Dawley(SD)大鼠建立ALI模型后用PA治疗。通过计算肺湿/干(W/D)比率分析肺水肿改变,通过酶联免疫吸附测定(ELISA)检测促炎细胞因子肿瘤坏死因子(TNF-α)、白介素1β(IL-1β)、白介素6(IL-6)的水平,通过炎症细胞计数和髓过氧化物酶(MPO)活性检测中性粒细胞浸润,通过CCK-8检测BEAS-2B细胞增殖,通过蛋白质免疫印迹(WB)检测了Keap1、Nrf2、HO-1蛋白表达,还检测了铁死亡相关标志物的水平。结果 与对照组相比,LPS诱导ALI加重了幼鼠炎症反应和肺水肿。与LPS组对比,PA保护了幼鼠免受LPS诱导的ALI导致的肺水肿、炎症浸润和铁死亡的损害。PA抑制LPS诱导的支气管上皮BEAS-2B细胞中的铁死亡和炎症。铁积累加重LPS诱导的ALI损伤。与Fe+LPS组相比,PA能缓解Fe堆积导致的炎症。而且PA可以上调Keap1-Nrf2/HO-1通路。结论 PA通过Keap1-Nrf2/HO-1途径减弱LPS诱导的ALI铁死亡,并且是ALI有希望的新型治疗候选药物。Objective To investigate the effect and mechanism of pachymaric acid(PA)on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in rats and bronchial epithelial BEAS-2B cells.Methods Young Sprague-Dawley(SD)rats were induced by LPS to establish ALI model and treated with PA.The change of pulmonary edema was analyzed by calculating the lung wet/dry(W/D)ratio,and the levels of pro-inflammatory cytokines tumor necrosis factor(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay(ELISA).Neutrophil infiltration was detected by inflammatory cell count and myeloperoxidase(MPO)activity,BEAS-2B cell proliferation was detected by CCK-8,Keap1,Nrf2,and HO-1 protein expression were detected by western blot(WB),and the levels of ferroptosis-related markers were also detected.Results Compared with the control group,LPS-induced ALI increased inflammation and pulmonary edema.Compared with the LPS group,PA protected the young rats from pulmonary edema,inflammatory infiltration,and ferroptosis which were caused by LPS-induced ALI.PA inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial BEAS-2B cells.Iron accumulation aggravated LPS-induced ALI injury.Compared with the Fe+LPS group,PA could relieve the inflammation caused by iron accumulation.Moreover,PA could up-regulate the Keap1-Nrf2/HO-1 pathway.Conclusion PA can attenuate LPS-induced ferroptosis of ALI through Keap1-Nrf2/HO-1 pathway,and it is a promising new therapeutic candidate for ALI.

关 键 词：急性肺损伤 铁死亡 氧化应激 脂多糖 炎症 

分 类 号：R285.5[医药卫生—中药学]