白花前胡甲素通过铁蛋白抑制中性粒细胞炎症反应及其在脓毒症中的作用  

Praeruptorin A inhibits neutrophil inflammation through ferritin and its role in sepsis

作　　者：俞鹏超 郑虹 胡一凡 杨舟鑫[2] 余泽佳 夏锦楠 韩海英 郭冬阳 Yu Pengchao;Zheng Hong;Hu Yifan;Yang Zhouxin;Yu Zejia;Xia Jinnan;Han Haiying;Guo Dongyang(School of Medicine,Hangzhou City University,Hangzhou 310015,China;Intensive Care Unit,Zhejiang Hospital,Hangzhou 310013,China)

机构地区：[1]浙大城市学院医学院,杭州310015 [2]浙江医院重症医学科,杭州310013

出　　处：《中华微生物学和免疫学杂志》2025年第3期248-255,共8页Chinese Journal of Microbiology and Immunology

基　　金：浙江省自然科学基金(LTGD24H190001)。

摘　　要：目的探究白花前胡甲素(praeruptorin A,PA)是否通过抑制铁蛋白的表达减轻炎症反应,从而改善脓毒症引起的炎症性损伤。方法C57BL/6小鼠腹腔注射脂多糖(lipopolysaccharide,LPS)构建脓毒症模型;PA干预6和12 h后,ELISA检测血清中炎症因子IL-6和TNF-α的表达变化;72 h取肾脏组织进行HE染色,观察炎性细胞浸润和组织损伤情况。将人中性粒细胞分为对照组、LPS组、铁蛋白组和LPS+铁蛋白组,干预12 h,qRT-PCR检测炎症因子IL-6和TNF-α的mRNA水平表达变化。为观察PA对炎症因子及铁蛋白表达的影响,将人中性粒细胞分为对照组、LPS组、LPS+PA(2/3/4μmol/L)组,12 h后qRT-PCR检测IL-1β、IL-6、TNF-α和铁蛋白的mRNA表达水平;ELISA法检测上清液中IL-1β、IL-6和TNF-α的分泌水平;Western blot检测铁蛋白表达水平。结果脓毒症过程中伴随炎性细胞大量募集、组织损伤及炎症因子IL-6和TNF-α的显著升高(P<0.01),PA可显著抑制小鼠血清中炎症因子的分泌(P<0.01)并改善组织损伤。在人中性粒细胞模型中,铁蛋白显著上调了炎症因子IL-6和TNF-α的mRNA表达水平(P<0.01);LPS单独刺激显著上调了IL-1β、IL-6、TNF-α和铁蛋白的mRNA及蛋白质表达水平(P<0.01),而PA(3/4μmol/L)与LPS共刺激后显著降低了这些炎症因子及铁蛋白的mRNA及蛋白质表达水平(P<0.01)。分子对接证明PA和铁蛋白存在相互作用位点。结论PA能够显著改善脓毒症中的炎症因子释放和组织损伤,其机制可能是通过调控铁蛋白的表达抑制脓毒症中的炎症反应。ObjectiveTo investigate the potential of praeruptorin A(PA)in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.MethodsC57BL/6 mice were intraperitoneally injected with lipopolysaccharide(LPS)to establish the model of sepsis.After 6 and 12 h of PA intervention,serum levels of inflammatory cytokines IL-6 and TNF-αwere measured by ELISA.Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage.Human neutrophils were divided into four groups:control,LPS,ferritin,and LPS+ferritin groups.After 12 h of intervention,qRT-PCR was used to detect the expression of IL-6 and TNF-αmRNA.In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin,human neutrophils were grouped into control,LPS,and LPS+PA(2/3/4μmol/L)groups.After 12 h of intervention,qRT-PCR was performed to measure the expression of IL-1β,IL-6,TNF-α,and ferritin mRNA;ELISA was used to quantify the levels of IL-1β,IL-6,and TNF-αin culture supernatants;Western blot was used to analyze the expression of ferritin.Molecular docking was conducted to verify interactions between PA and ferritin.ResultsSignificant inflammatory cell recruitment,tissue damage,and elevated serum levels of IL-6 and TNF-α(P<0.01)were observed in mice with LPS-induced sepsis.PA significantly inhibited cytokine secretion(P<0.01)and alleviated tissue injury in sepsis mice.In human neutrophil models,ferritin upregulated the expression of IL-6 and TNF-αmRNA(P<0.01);LPS stimulation alone increased the expression of IL-1β,IL-6,TNF-α,and ferritin at both mRNA and protein levels(P<0.01),while co-stimulation with PA(3/4μmol/L)significantly reversed the aforementioned results(P<0.01).Molecular docking confirmed there were interaction sites between PA and ferritin.ConclusionPA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis,and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.

关 键 词：脓毒症 白花前胡甲素 中性粒细胞 炎症因子 铁蛋白 

分 类 号：R459.7[医药卫生—急诊医学]