中国临床药理学与治疗学2025，Vol.30Issue(2)：209-215,7.DOI:10.12092/j.issn.1009-2501.2025.02.007
当归黄芪超滤物介导Jagged1/Notch1通路抑制成纤维细胞转分化抗放射性心肌纤维化的作用机制研究
Radix angelica sinensis and astragalus mongholicus extract mediating the Jagged1/Notch1 pathway to inhibit fibroblast transdifferentia-tion and resist radiation induced myocardial fibrosis
摘要
Abstract
AIM:To study the mechanism of ac-tion of radix angelica sinensis and astragalus mong-holicus extract(RAS-AM)in inhibiting fibroblast transdifferentiation(CMT)and preventing radiation-induced myocardial fibrosis(RIMF)via the Jagged1/Notch1 pathway.METHODS:Sixty male Wistar rats were randomly divided into blank group,model group,benazepril hydrochloride group,low dose RAS-AM group,medium dose RAS-AM group,and high dose RAS-AM group,with 10 rats in each group.Except for the blank group,all other groups were induced with high-energy radiation at a dose of 38 Gy to establish RIMF models.The blank group and the model group received sterile distilled water by gavage,and the other groups received medica-tion for 4 weeks of intervention:benazepril hydro-chloride group(1.0 mg·kg-1·d-1),low dose RAS-AM group(150 mg·kg-1·d-1),medium dose RAS-AM group(300 mg·kg-1·d-1),and high dose RAS-AM group(600 mg·kg-1·d-1).The general condition of rats,the ultrastructure of myocardial tissue were observed using electron microscopy,changes in myocardial tissue fibers using Masson staining,and CMT related protein Vimentin and α-SMA expres-sion using immunohistochemical staining tech-niques.ELISA was used to detect serum inflammato-ry factors IL-6 and TNF-α in rats.The levels of cTnI and ST2,and the expression of Jagged1 and Notch1 were detected by Western blot.RESULTS:Com-pared with the blank group,the model group rats exhibited symptoms such as mental fatiguem an-orexiam and loose stools;The arrangement of some myofibrils in the myocardium is disordered,with dis-solution and breakage of myofibrilsm abnormal Z-line structure in some partsm disordered mitochon-drial arrangement,rupture of mitochondrial mem-branem,and rupture or disappearance of mitochon-drial ridge structure in some parts.A large amount of collagen fibers proliferate and deposit in the myo-cardium,and the fibrotic area significantly increases(P<0.01);The expression of myocardial tissue Vi-mentin α-SMA protein increased(P<0.05),while the expression of Jagged1 and Notch1 proteins de-creased(P<0.05);serum IL-6 and TNF-α,the expres-sion of inflammatory factors such as cTnI and ST2 in-creased(P<0.05).compared with the model group,the RAS-AM and benazepril hydrochloride groups showed varying degrees of improvement in general conditions;the pathological changes of myocardial ultrastructure have been improved,and myocardial fibrosis has been alleviated;The area of collagen fi-bers significantly decreased(P<0.01);Myocardial tis-sue Vimentin α-SMA protein expression decreased(P<0.05),while Jagged1 and Notch1 expression in-creased(P<0.05);Serum IL-6 and TNF-α,The expres-sion of inflammatory factors such as cTnI and ST2 decreased(P<0.05).CONCLUSION:RAS-AM may al-leviate RIMF by intervening in the Jagged1/Notch1 pathway to inhibit CMT.The specific mechanism still needs further investigation关键词
当归黄芪超滤物/Jagged1/Notch1通路/成纤维细胞转分化/放射性心肌纤维化Key words
radix angelica sinensis and astragalus mongholicus extract/Jagged1/Notch1 pathway/fi-broblast transdifferentiation/radiation induced myocardial fibrosis分类
药学引用本文复制引用
李雯,蒋虎刚,王新强,李应东,刘凯,赵信科..当归黄芪超滤物介导Jagged1/Notch1通路抑制成纤维细胞转分化抗放射性心肌纤维化的作用机制研究[J].中国临床药理学与治疗学,2025,30(2):209-215,7.基金项目
国家自然科学基金项目(82360926) （82360926）
中医药传承与创新"百千万"人才工程(岐黄工程)青年岐黄学者基金资助项目 （岐黄工程）
国家中医药管理局"李应东全国名中医传承工作室"建设项目(国中医药办人教函[2022]5号) （国中医药办人教函[2022]5号）
甘肃省科技重大专项计划(20ZD7FA002) （20ZD7FA002）
2021年度"双一流"科研重点项目(GSSYLXM-05-ZXYJH-5) （GSSYLXM-05-ZXYJH-5）
甘肃省中医药防治重大疾病科研课题项目(GZKZD-2018-02) （GZKZD-2018-02）
甘肃省教育科技创新项目教育揭榜挂帅基金资助项目(2021jyjbgs-03) （2021jyjbgs-03）
白银市科技计划项目(2022-2-50Y) （2022-2-50Y）
甘肃中医药大学第三附属医院院内课题(2022YK-11) （2022YK-11）
