首页|卷柏总黄酮通过调节Nrf2/HO-1信号通路减轻机械通气相关性肺损伤的机制

卷柏总黄酮通过调节Nrf2/HO-1信号通路减轻机械通气相关性肺损伤的机制

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目的 探讨卷柏总黄酮(TFST)调控Nrf2/HO-1信号通路对机械通气相关性肺损伤(VALI)的影响.方法 选取健康SPF级雄性SD大鼠40只,采用随机数字表法分为4组,每组10只.对照组仅对大鼠插管不进行机械通气;模型组采用潮气量30 mL/kg,通气频率60次/min,吸氧浓度FiO2 21%,吸呼比1∶2,通气时间4 h制备大鼠VALI模型;TFST组于造模前2周开始每天1次卷柏总黄酮混悬液800 mg/kg灌胃给药;ML385组,卷柏总黄酮预保护2周并在机械通气前1 h,将ML385(Nrf2抑制剂)30 mg/kg注射于大鼠腹腔.结束后处死大鼠并收集大鼠支气管肺泡灌洗液(BALF)使用ELISA法测定其中IL-6及TNF-α浓度;且收集大鼠肺组织进行HE染色观察其病理学变化后作肺损伤评分,比较各组大鼠肺组织湿重干重比(W/D),检测肺组织中丙二醛(MDA)水平,WST-8法测定肺组织超氧化物歧化酶(SOD)水平,采用 Western blot法检测肺组织Nrf2及HO-1蛋白的水平.结果 与对照组比较,模型组的肺组织 W/D值及MDA含量,肺损伤评分及BALF中IL-6、TNF-α升高,肺组织中SOD含量,Nrf2、HO-1蛋白水平降低(均P<0.05).与模型组比较,TFST组的肺组织 W/D值及MDA含量降低,肺损伤减轻及BALF中IL-6、TNF-α降低,SOD含量,Nrf2、HO-1蛋白水平增加(P<0.05);ML385组则较TFST组大鼠肺损伤加重,肺组织 W/D值及MDA含量,BALF中IL-6、TNF-α升高,SOD含量,Nrf2、HO-1蛋白水平降低(P<0.05).结论 卷柏总黄酮可通过调节Nrf2/HO-1通路激活抗氧化途径改善大鼠机械通气相关肺损伤.
Study on the mechanism of total flavonoids of selaginella tamariscina vulgaris reducing mechanical ventilation related lung injury by regulating Nrf2/HO1 signal pathway
Objective To investigate the effect of total flavonoids of selaginella officinalis(TFST)regulating the Nrf2/HO-1 signaling pathway on mechanical ventilation associated lung injury(VALI).Methods Forty healthy SPF grade male SD rats were selected and randomly divided into four groups(10 in each group)using a random number table method.The control group only received intubation without mechanical ventilation;In the model group,a rat VALI model was prepared using tidal volume of 30 mL/kg,ventilation frequency of 60 times/min,oxygen uptake concentration of 21% FiO2,inhalation to exhalation ratio of 1∶2,and ventilation time of 4 hours;TFST group,starting from 2 weeks before modeling,was orally administered 800 mg/kg of total flavonoids suspension of selaginella officinalis once a day;ML385 group,pre protected with total flavonoids of selaginella vulgaris for 2 weeks,and ML385(Nrf2 inhibitor)30mg/kg was injected into the intraperitoneal cavity of rats 1 hour before mechanical ventilation.After the end of the experi-ment,the rats were euthanized and their bronchoalveolar lavage fluid(BALF)was collected for the determination of IL-6 and TNF-α using ELISA concentration.And collect rat lung tissue for HE staining to observe its pathological changes,and then score lung injury.Compared the wet to dry weight ratio(W/D)of lung tissue in each group of rats,detected the level of malondialdehyde(MDA)in lung tissue,measured the level of superoxide dismutase(SOD)in lung tissue u-sing WST-8 method,and detected the levels of Nrf2 and HO-1 protein in lung tissue using Western blot method.Results Compared with the control group,the W/D value and MDA content of lung tissue,lung injury score,and IL-6 and TNF-α in BALF in the model group were elevated.SOD content,Nrf2 and HO-1 protein levels in lung tissue decreased(P<0.05).Compared with the model group,the W/D value and MDA content of lung tissue in the TFST group decreased,lung injury decreased,and IL-6 and TNF-α in BALF decreased decreased.SOD content,Nrf2,HO-1 protein levels in-creased(P<0.05).The ML385 group had more severe lung injury compared to the TFST group,with W/D values and MDA content in lung tissue,as well as IL-6 and TNF-α in BALF elevated,SOD content and Nrf2 and HO-1 protein lev-els decreased(P<0.05).Conclusion The total flavonoids of selaginella can improve mechanical ventilation related lung injury in rats by regulating the Nrf2/HO-1 pathway and activating antioxidant pathways.

Mechanical ventilationLung injuryTotal flavonoids of selaginella tamariscinaHO-1Nrf2Oxida-tive stress

肖国素、余洲、陈丽娜、吴玉婷、曹珊、张蕾、黄妮雯

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贵州医科大学附属医院呼吸与危重症医学科,贵州贵阳 550001

贵州医科大学临床医学院,贵州贵阳 550004

贵阳市公共卫生救治中心,贵州贵阳 550000

贵州医科大学附属医院病理科,贵州贵阳 550001

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机械通气 肺损伤 卷柏总黄酮 HO-1 Nrf2 氧化应激

2025

西部医学
四川

西部医学

影响因子:1.352
ISSN:1672-3511
年,卷(期):2025.37(1)