五味子醇乙经Nrf2-GPX4信号通路防治肠道辐照损伤  

Schisandrol B protects intestinal cells against irradiation-inducedinjury via Nrf2-GPX4 signaling pathway

作　　者：吴泽坤 胡昌坤 张亮亮 廖泽彬 高月 WU Ze-kun;HU Chang-kun;ZHANG Liang-liang;LIAO Ze-bin;GAO Yue(School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China;Academy of Military Medical Sciences,Beijing 100850,China;School of Pharmacy,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;State Key Laboratory of Kidney Diseases,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]广东药科大学药学院,广东广州510006 [2]军事医学研究院,北京100850 [3]天津中医药大学药学院,天津301617 [4]中国人民解放军总医院肾脏疾病国家重点实验室,北京100853

出　　处：《中国药理学通报》2024年第12期2236-2246,共11页Chinese Pharmacological Bulletin

基　　金：国家自然科学基资助项目(No 82103776,82192911)。

摘　　要：目的 探讨五味子醇乙(schisandrol B,Sol B)对肠道辐照损伤的防治作用及其潜在机制。方法 通过4Gy辐照建立小鼠肠道损伤模型。利用免疫组化、免疫荧光染色和ELISA检测等方法评估辐照后小鼠肠道中的DNA损伤、细胞凋亡、炎症反应及氧化应激水平。评价Sol B对肠道损伤的保护作用,并探讨其涉及的铁死亡和炎症反应途径机制。结果 Sol B明显提高了辐照后肠道细胞的存活率。肠道组织中DNA损伤积累、凋亡率及炎症因子水平均受到明显抑制。Sol B能恢复辐照后ZO-1和Occuldin蛋白的水平,表明Sol B能改善辐照后肠道结构损伤。机制上,Sol B的辐照防护作用与Nrf2介导的铁死亡抵抗密切相关。结论 Sol B能有效减轻辐照导致的肠道损伤,其主要经Nrf2介导的GPX4激活拮抗辐照导致的铁死亡,有望用于放疗或核事故中肠道损伤的防治。Aim To investigate the radio-protective effect of schisandrol B(Sol B)underlying mechanism in alleviating gastrointestinal(GI)toxicity and intestinal damage induced by irradiation(IR)exposure during radiotherapy against abdominal and pelvic malignancies or the nuclear accident.Methods The mouse intestinal injury model was established through 4Gy irradiation.Immunohistochemistry,immunofluorescence staining,ELISA were used to measure DNA damage,apoptosis,inflammatory reaction,and oxidative stress in the intestine of mice after irradiation.The protective effect of Sol B on intestines injury was evaluated,and the mechanism of the related oxidative stress and inflammatory response pathway was discussed.Results Sol B significantly improved the survival rates of intestinal cells upon IR exposure.The accumulation of DNA damage,apoptosis rate,and inflammatory factors in intestinal tissues were significantly inhibited.The decreased levels of ZO-1 and occludin induced IR injury were rescued by Sol B,indicating the improvement of intestinal structure.The radio-protective activities of Sol B were involved in the stimulation of Nrf2 and the subsequent ferroptosis surveillance.Conclusion Sol B demonstrates a promising agent to ease intestinal injury during radiotherapy or nuclear accidents,in which GPX4 related ferroptosis surveillance mediated by Nrf2 is involved in the radio-protective effect of Sol B.

关 键 词：五味子醇乙 肠道损伤 电离辐照 NRF2 铁死亡 炎症 

分 类 号：R-332[医药卫生] R284.1R322.45R591.1R641R818.74