山东医药2024，Vol.64Issue(15)：13-18,6.DOI:10.3969/j.issn.1002-266X.2024.15.003
槲皮素预处理ALI大鼠肺组织损伤、炎症/氧化应激反应、铁死亡及Nrf2/HO-1信号通路激活情况观察
Effects of quercetin pretreatment on lung tissue damage,inflammatory/oxidative stress responses,ferroptosis,and Nrf2/HO-1 signaling pathway activation in ALI rats
摘要
Abstract
Objective To observe the effects of quercetin pretreatment through intragastric administration on lung tissue injury,inflammatory response,oxidative stress response,ferroptosis,and the activation of the Nrf2/HO-1 signaling pathway in rats with lipopolysaccharide(LPS)-induced acute lung injury(ALI)in order to investigate quercetin's preven-tive effect and mechanism on ALI.Methods Twenty-four Sprague-Dawley rats were divided into the low-dose,medium-dose,and high-dose quercetin groups,positive control group(dexamethasone),model group,and normal control group,respectively.Rats in the low-dose,medium-dose,and high-dose quercetin groups received quercetin via gavage at doses of 25,50,and 100 mg/kg,respectively,once a day for 7 consecutive days.On the fourth day of quercetin treatment,5 mg/kg LPS was instilled into the trachea of the rats.Rats in the positive control group received dexamethasone at a dose of 1.04 mg/kg via gavage,following the same treatment regimen as the quercetin groups.Rats in the model group received normal saline via gavage once a day for 7 consecutive days,with the same additional treatments as the quercetin groups.Rats in the normal control group received normal saline via gavage for 7 consecutive days.After the final administration,lung tissue injury(lung function,pathological changes,positive expression rate of fibrous tissues,and apoptosis rate of al-veolar epithelial cells),inflammatory response[levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and in-terleukin-1β(IL-1β)]in bronchoalveolar lavage fluid,oxidative stress response[levels of superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA)in bronchoalveolar lavage fluid,and ROS in lung tissue],ferroptosis(Fe2+levels),and activation of the Nrf2/HO-1 signaling pathway[levels of nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),superoxide dismutase 2(SOD2),and catalase(CAT)proteins in lung tissues]were observed in each group.Results Compared with the normal control group,PaCO2 level increased,PaO2 and SaO2 levels de-creased,alveolar epithelial cells were degenerated and necrotic in lung tissues,the positive expression rate increased in fi-ber tissues,the apoptosis rate increased,the levels of TNF-α,IL-6,and IL-1β in alveolar lavage fluid increased,SOD and GSH levels decreased,MDA and Fe2+levels increased,and ROS levels in lung tissues increased in the model group(all P<0.01).Compared with the model group,PaCO2 in the medium-dose and high-dose quercetin groups and positive control group decreased(all P<0.05),and PaO2 and SaO2 levels increased in the high-dose quercetin group(all P<0.05);the inflammatory infiltration and fibrous hyperplasia of lung tissue were significantly reduced in the high-dose quer-cetin group and positive control group,and the physiological structure of the alveolar was restored to normal;the positive fi-ber expression rates of the low-,medium-,and high-dose quercetin groups and the positive control group decreased(all P<0.05)with the lowest positive fiber expression rate in the high-dose quercetin group;the apoptosis rates decreased(all P<0.01),the levels of TNF-α,IL-6,and IL-1β in alveolar lavage fluid decreased,the levels of SOD and GSH increased,the levels of MDA and Fe2+decreased,and the levels of ROS decreased in the low-,medium-,and high-dose quercetin groups and positive control group(all P<0.01).Compared with the normal control group,the protein expression levels of CAT,HO-1,Nrf2,and SOD2 in the lung tissues of the model group were lower(all P<0.01);compared with the model group,the protein expression levels of CAT,HO-1,Nrf2,and SOD2 in the lung tissues of the medium-dose and high-dose quercetin groups and the positive control group were higher(all P<0.05).Conclusions Quercetin pretreatment via ga-vage reduces lung tissue injury,inflammatory response,oxidative stress response,and ferroptosis,and activates the Nrf2/HO-1 signaling pathway in rats with LPS-induced ALI.Quercetin pretreatment can prevent LPS-induced ALI in rats,possi-bly by inhibiting inflammatory response,oxidative stress response,and ferroptosis,and the protective effects of quercetin may be mediated through up-regulation of the Nrf2/HO-1 signaling pathway.Both 50 mg/kg and 100 mg/kg doses of quer-cetin can effectively prevent LPS-induced ALI in rats,with the better effect in the 100 mg/kg dose.关键词
槲皮素/急性肺损伤/铁死亡/炎症反应/氧化应激反应/核因子红细胞2相关因子2/血红素加氧酶1信号通路Key words
quercetin/acute lung injury/ferroptosis/inflammatory response/oxidative stress response/nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 signaling pathway分类
医药卫生引用本文复制引用
李雪,李博,谈彬,马磊..槲皮素预处理ALI大鼠肺组织损伤、炎症/氧化应激反应、铁死亡及Nrf2/HO-1信号通路激活情况观察[J].山东医药,2024,64(15):13-18,6.基金项目
宁夏急救医学研究人才小高地建设项目(宁人社函(2019)463号). （宁人社函(2019）
