摘要
目的探讨苍术醇提物通过抑制铁死亡对急性肺损伤(ALI)大鼠的改善作用。方法将50只雄性SD大鼠随机分为空白组、模型组、Fer-1组(铁死亡抑制剂,10 mg/kg)和苍术醇提物低、高剂量组(341.7、2517.4 mg/kg),每组10只,灌胃给药7 d后,除空白组气管滴注无菌PBS外,其余各组均气管滴注LPS(5 mg/kg)建立ALI模型,12 h后处死大鼠,收集肺泡灌洗液与肺组织。ELISA法检测肺泡灌洗液TNF-α、IL-1β、IL-6水平和肺组织Fe^(2+)、Fe^(3+)、MDA、4-HNE、GSH水平和SOD活性;HE染色观察肺部病理变化;化学荧光法检测肺组织ROS水平;RT-qPCR、Western blot和免疫组化法检测肺组织Nrf2、SLC7A11、GPX4 mRNA和蛋白表达。结果与空白组比较,模型组大鼠肺泡灌洗液TNF-α、IL-1β、IL-6水平升高(P<0.01);肺组织出现明显肺泡萎缩、肺泡壁增厚以及炎症浸润的情况;肺组织SOD活性和GSH水平降低(P<0.05),ROS、MDA、4-HNE、Fe^(2+)、Fe^(3+)水平升高(P<0.05);肺组织Nrf2、SLC7A11、GPX4蛋白及mRNA表达均降低(P<0.05,P<0.01)。与模型组比较,苍术醇提物高剂量组和Fer-1组大鼠肺泡灌洗液TNF-α、IL-1β、IL-6水平降低(P<0.05);肺组织病理损伤情况得到改善;肺组织SOD活性和GSH水平升高(P<0.05,P<0.01),ROS、MDA、4-HNE、Fe^(2+)、Fe^(3+)水平降低(P<0.05);苍术醇提物高剂量组肺组织Nrf2、SLC7A11、GPX4蛋白及mRNA表达均升高(P<0.05)。结论苍术醇提物可能通过调控Nrf2/SLC7A11/GPX4信号通路来抑制铁死亡过程,从而改善大鼠急性肺损伤。
AIM To investigate the ameliorative effect of ethanolic extract of Atractylodis Rhizoma on acute lung injury(ALI)rats by inhibiting ferroptosis.METHODS Fifty male SD rats were randomly divided into blank group,model group,low-dose and high-dose groups of ethanolic extract of Atractylodis Rhizoma(341.7 and 2517.4 mg/kg)and Fer-1 group(ferroptosis inhibitor,10 mg/kg),with 10 rats in each group.After 7 days of intragastric administration,the ALI model was established by intratracheal instillation of LPS(5 mg/kg)except for sterile PBS in blank group.The rats were sacrificed 12 hours later,and the alveolar lavage fluid and lung tissue were collected.The levels of TNF-α,IL-1β,IL-6 in alveolar lavage fluid and the levels of Fe^(2+),Fe^(3+),MDA,4-HNE,GSH and SOD activity in lung tissue were detected by ELISA;HE staining was used to observe the pathological changes of lung;ROS levels in lung tissue were detected by chemical fluorescence method;RT-qPCR,Western blot and immunohistochemistry were used to detect the mRNA and protein expressions of Nrf2,SLC7A11 and GPX4 in lung tissue.RESULTS Compared with the blank group,the levels of TNF-α,IL-1β and IL-6 in the alveolar lavage fluid of the model group were increased(P<0.01);the lung tissue showed obvious alveolar atrophy,alveolar wall thickening and inflammatory infiltration;the SOD activity and GSH level in lung tissue decreased(P<0.05),while the levels of ROS,MDA,4-HNE,Fe^(2+),Fe^(3+)increased(P<0.05);the protein and mRNA expressions of Nrf2,SLC7A11,GPX4 in lung tissue were decreased(P<0.05,P<0.01).Compared with the model group,the levels of TNF-α,IL-1β and IL-6 in alveolar lavage fluid of rats in the high-dose ethanolic extract of Atractylodis Rhizoma group and Fer-1 group were decreased(P<0.05);the pathological injury of lung tissue was improved;SOD activity and GSH level in lung tissue increased(P<0.05,P<0.01),while ROS,MDA,4-HNE,Fe^(2+),Fe^(3+)levels decreased(P<0.05);the protein and mRNA expressions of Nrf2,SLC7A11,GPX4 in lung tissue of high-dose ethanolic extract of Atractylodis Rhizoma group were increased(P<0.05).CONCLUSION The ethanolic extract of Atractylodis Rhizoma may inhibit the process of ferroptosis by regulating the Nrf2/SLC7A11/GPX4 signaling pathway,thereby improving acute lung injury in rats.
作者
严世豪
石坤
温佳文
张金莲
龚文慧
辛力
张文
李志强
YAN Shi-hao;SHI Kun;WEN Jia-wen;ZHANG Jin-lian;GONG Wen-hui;XIN Li;ZHANG Wen;LI Zhi-qiang(Jiangxi University of Chinese Medicine,Nanchang 330004,China;The Second People’s Hospital of Jingdezhen,Jingdezhen 333000,China)
出处
《中成药》
2026年第2期416-423,共8页
Chinese Traditional Patent Medicine
基金
江西省中医药管理局科技计划项目(2024A0153)
江西中医药大学博士科研启动基金(2024BSZR053)。
