摘要
目的:研究敦煌神仙粥对放射性脑损伤的保护作用,探讨其与氧化应激和糖原合成酶激酶-3β(GSK-3β)/核因子E2相关因子2(Nrf2)信号通路的关系。方法:40只SD大鼠随机分为正常对照组、模型对照组、神仙粥4.8、9.6、19.2 g/kg组,每组各8只。常规饲养7 d后,除正常对照组外,其余各组大鼠脑部给予20 Gy X射线单次照射,照射后各组给予相应药物或生理盐水灌胃,连续给药14 d。干预完成后水迷宫检测大鼠认知功能;比色法检测脑组织丙二醛(MDA)及谷胱甘肽(GSH)的含量评估脑内氧化应激程度;免疫荧光法测定脑组织活性氧(ROS)水平;ELISA法检测血清肿瘤坏死因子-α(TNF-α)、白介素1-β(IL-1β)含量变化;HE染色法观察大鼠脑组织形态学改变情况;Western blot法检测大鼠脑组织GSK-3β、磷酸化糖原合成酶激酶-3β(p-GSK-3β)、Nrf2蛋白的表达。结果:与正常对照组比较,模型对照组大鼠的逃避潜伏期和空间探索时间明显延长,血清TNF-α、IL-1β、脑组织MDA含量、ROS水平显著升高,GSH的含量显著降低,脑组织p-GSK-3β蛋白表达上调,Nrf2蛋白表达下调,体质量显著降低(P<0.01);与模型对照组比较,神仙粥9.6 g/kg组大鼠的逃避潜伏期和空间探索时间缩短,血清TNF-α、IL-1β、脑组织MDA含量、ROS水平在辐射后不同时间点均明显降低,GSH含量明显升高,脑组织p-GSK-3β蛋白表达明显下调,Nrf2蛋白表达显著上调,体质量明显增加(P<0.05或P<0.01)。结论:神仙粥对X射线所致大鼠脑损伤具有保护作用,其可能通过下调p-GSK-3β蛋白表达及降低TNF-α、IL-1β含量,上调Nrf2蛋白表达,从而调节氧化应激及炎症反应,缓解脑组织辐射损伤。
Objective:To study the protective effect of Dunhuang Shenxian(敦煌神仙)porridge on radiation-induced brain injury and its relationship with oxidative stress and glycogen synthase kinase-3β(GSK-3β)/nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Methods:Forty SD rats were randomly divided into five groups:the normal control,the model control,and Shenxian porridge(4.8,9.6,and 19.2 g/kg),with 8 rats in each group.After 7 days of routine feeding,the brains of rats in other groups except the normal control group were irradiated with a single dose of 20 Gy X-ray.After irradiation,the rats in Shenxian porridge groups were administered with Shenxian porridge at corresponding doses by gavage,and those in other groups were administered with the same amount of saline by gavage for 14 days.After the intervention,the cognitive function of rats was examined by the Morris water maze test,and the protein levels of CSK-3β,phosphorylated GSK-3β(p-CSK-3β),and Nrf2 in the brain tissues were determined by Western blot.Reactive oxygen species(ROS)in the brain tissue was detected by immunofluorescence.The levels of malondialdehyde(MDA)and glutathione(GSH)in the brain tissues were measured by colorimetry.The levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in the serum were determined by ELISA.Hematoxylin-eosin staining was employed to observe the histomorphological changes of the rat brain.Results:Compared with the normal control group,the rats in the model control group showed prolonged escape latency and space exploration time,elevated levels of TNF-α,IL-1β,ROS,and MDA,up-regulated expression of p-GSK-3β,a lowered level of GSH,down-regulated expression of Nrf2,and a decreased body weight(P<0.01).Compared with the model control group,the rats in Shenxian porridge(9.6 g/kg)group showed shortened escape latency and space exploration time,lowered levels of TNF-α,IL-1β,ROS,and MDA at different time points after radiation,down-regulated expression of p-GSK-3β,an elevated level of GSH,up-regulated expression of Nrf2,and an increased body weight(P<0.05 or P<0.01).Conclusion:Shenxian porridge has a protective effect on the brain injury induced by X-ray.It can down-regulate the expression of p-GSK-3β,lower the levels of TNF-αand IL-1β,and up-regulate the expression of Nrf2,thereby regulating oxidative stress and inflammation to alleviate the radiation-induced injury in the brain tissue.
作者
刘秀珠
马礼科
马玉
武兵兵
王燕如
李佳蔚
何进鹏
谢小冬
刘永琦
LIU Xiuzhu;MA Like;MA Yu;WU Bingbing;WANG Yanru;LI Jiawei;HE Jinpeng;XIE Xiaodong;LIU Yongqi(Key Laboratory of Dunhuang Medicine of Ministry of Education,Gansu University of Chinese Medicine,Lanzhou 730050;Institute of Genetics,School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000;Biomedical Center,Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou 730000;The 940th Hospital of PLA,Lanzhou 730000;The Fourth Sanatorium for Retired Cadres,Lanzhou Military Command of Gansu Province,Lanzhou 730000)
出处
《中药药理与临床》
北大核心
2025年第7期32-37,共6页
Pharmacology and Clinics of Chinese Materia Medica
基金
高校科研创新平台重大培育项目(编号:2024CXPT-08)
甘肃中医药大学研究生创新基金资助项目(2021CX27)
2023年甘肃省海智基地特色示范项目“健康管理基因检测产品的研发”(编号:GSHZTS 2022-04)
甘肃省科技重大专项(编号:22ZD1FA001)。
