摘要
目的探讨ROS/GSH/GPx4轴介导的心肌铁死亡在放射性心肌纤维化中的作用机制及当归黄芪超滤物的干预作用。方法50只大鼠随机分为5组。除空白组外,其余各组大鼠均接受X射线单次局部胸部照射建立放射性心肌纤维化模型。辐射后,当归黄芪超滤物各组大鼠分别灌胃给药30 d后,用小动物超声评价心功能;比色法检测SOD、GSH、MDA及Fe^(2+)活性;免疫荧光检测ROS表达;HE、Masson染色观察病理变化及纤维化;透射电镜观察心肌超微结构;Western blot检测铁死亡及纤维化蛋白表达。结果与空白组比较,模型组LVEF和LVFS值降低;Fe^(2+)、MDA、ROS水平上升,SOD、GSH水平下降;HE及Masson显示有炎性细胞聚集及胶原纤维沉积;透射电镜显示受损线粒体数量增多、排列紊乱,形态不规则、变小、嵴紊乱;Western blot显示α-SMA、Collagen I、NOX1蛋白表达升高,GPx4、FTH1蛋白表达降低;与模型组比较,当归黄芪超滤物组大鼠心功能改善,ROS、抗氧化指标恢复,Fe^(2+)水平降低;线粒体结构及纤维化程度减轻;α-SMA、Collagen I、NOX1蛋白表达下降,GPx4、FTH1蛋白表达上升。结论当归黄芪超滤物对放射性心肌纤维化具有抑制作用,其机制可能是通过调控ROS/GSH/GPx4轴抑制心肌铁死亡发挥作用。
Aim To investigate the mechanism of ROS/GSH/GPx4 axis-mediated cardiomyocyte iron death in myocardial fibrosis in radioactive rats and the intervention of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA).Methods Fifty Wistar rats were randomly divided into five groups of 10 rats in each.Except for the normal control group which was not irradiated,the rats in other groups were anaesthetised and received 40 Gy X-rays single local chest irradiation once to establish myocardial fibrosis in radioactive rats.After radiation,rats in each intervention group of RAS-RA were administered by gavage at doses of 0.12,0.24,and 0.48 g·kg^(-1),respectively,once/day for 30 consecutive days.After 30 consecutive days of administration,cardiac function of rats in each group was detected by small animal ultrasound;SOD,GSH,MDA and Fe^(2+)levels,indicators of oxidative stress,were detected by colorimetric method in cardiac tissue of each group;fluorescence intensity of reactive oxygen species(ROS)was detected by immunofluorescence in cardiac tissue;pathological morphology of cardiac tissue and fibrosis were observed by HE and Masson staining.And the rats in each group was used to observe the ultrastructural changes of myocardium by transmission electron microscopy.The protein expression levels of NOX1,GPx4,FTH1,CO1 andα-SMA in myocardial tissue were detected by Western blot.Results Compared with the blank group,the LVEF and FS values of rats in the model group were significantly reduced(P<0.05);Fe^(2+)level increased,MDA level increased,SOD and GSH level decreased(P<0.05);ROS level increased;HE and Masson showed that the cardiac cell morphology was irregularly arranged,with more inflammatory cell aggregation and collagen fibre deposition.Transmission electron microscopy showed that myofilament arrangement of cardiomyocytes in the model group was irregular and loosely arranged and disordered,myofilaments were broken and dissolved,the number of damaged mitochondria was significantly increased and disordered,m
作者
任春贞
陈其林
张启立
吕欣芳
支晓东
高翔
吴雪
李晓静
刘凯
赵信科
李应东
REN Chun-zhen;CHEN Qi-lin;ZHANG Qi-li;LYU Xin-fang;ZHI Xiao-dong;GAO Xiang;WU Xue;LI Xiao-jing;LIU Kai;ZHAO Xin-ke;LI Ying-dong(School of Traditional Chinese and Western Medicine,Gansu University of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China;Gansu Province Key Laboratory of Chinese Medicine for the Prevention and Treatment of Chronic Diseases,Gansu University of Chinese Medicine,Lanzhou 730000,China;Affiliated Hospital of Gansu University of Chinese Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,China;College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou 730000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2024年第4期723-730,共8页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 82260869,82360926)
甘肃教育揭榜挂帅项目(No 2021jyjbgs-03)
甘肃省中医药防治重大疾病专项(No GZKZD-2018-02)
甘肃省科技重大专项(No 20ZD7FA002)
甘肃省陇原青年创新创业人才项目
甘肃省青年科技基金(No 23JRRA1217)
2022年甘肃省优秀研究生“创新之星”基金(No 2022CXZX-736)。
关键词
当归黄芪超滤物
放射性心肌纤维化
铁死亡
氧化应激
ROS/GSH/GPx4轴
抗心肌纤维化
Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract
radiation-induced myocardial fibrosis
ferroptosis
oxidative stress
ROS/GSH/GPx4 axis
anti-myocardial fibrosis
