文献类型：期刊文献

中文题名：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

英文题名：Radix angelica sinensis and astragalus mongholicus extract mediating the Jagged1/Notch1 pathway to inhibit fibroblast transdifferentiation and resist radiation induced myocardial fibrosis

作者：李雯[1,3];蒋虎刚[1,3];王新强[2,3];李应东[1,2,3];刘凯[1,2,3];赵信科[1,2,3]

第一作者：李雯

机构：[1]甘肃中医药大学中西医结合学院,甘肃兰州730000;[2]甘肃中医药大学附属医院心血管中心,甘肃兰州730000;[3]甘肃省中医药防治慢性疾病重点实验室,甘肃兰州730000

第一机构：甘肃中医药大学中西医结合学院

年份：2025

卷号：30

期号：2

起止页码：209

中文期刊名：中国临床药理学与治疗学

外文期刊名：Chinese Journal of Clinical Pharmacology and Therapeutics

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金项目(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;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);甘肃省科技重大专项计划(20ZD7FA002);2021年度“双一流”科研重点项目(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);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);白银市科技计划项目(2022-2-50Y);甘肃中医药大学第三附属医院院内课题(2022YK-11)。

语种：中文

中文关键词：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

外文关键词：radix angelica sinensis and astragalus mongholicus extract;Jagged1/Notch1 pathway;fibroblast transdifferentiation;radiation induced myocardial fibrosis

摘要：目的:基于Jagged1/Notch1通路,研究当归黄芪超滤物(radix angelica sinensis and astragalus mongholicus extract,RAS-AM)抑制成纤维细胞转分化(cardiac fibroblast-myofibroblast transformation,CMT)抗放射性心肌纤维化(radiationinduced myocardial fibrosis,RIMF)的作用机制。方法:Wistar雄性大鼠60只随机分为空白组、模型组、盐酸贝那普利组、RAS-AM低剂量组、RAS-AM中剂量组、RAS-AM高剂量组,每组各10只,除空白组外,其余各组均采用高能射线诱导建立RIMF模型。空白组、模型组无菌蒸馏水灌胃,其余各组给药干预4周:盐酸贝那普利组(1.0 mg·kg^(-1)·d^(-1))、RAS-AM低剂量组(150 mg·kg^(-1)·d^(-1))、RAS-AM中剂量组(300 mg·kg^(-1)·d^(-1))、RAS-AM高剂量组(600 mg·kg^(-1)·d^(-1))。观察大鼠一般情况,采用电镜观察心肌组织超微结构,Masson染色观察心肌组织纤维变化,免疫组织化学染色技术检测CMT相关蛋白Vimentin、α-SMA的表达,ELISA法检测大鼠血清炎症因子IL-6、TNF-α、cTnI、ST2的水平,Western blot检测Jagged1、Notch1的表达。结果:与空白组比较,模型组大鼠均有精神萎靡、厌食、稀便等症状;心肌部分肌原纤维排列紊乱,肌原纤维溶解、断裂,部分Z线结构异常,线粒体排列紊乱、线粒体膜破裂、线粒体部分嵴结构断裂或消失,心肌大量胶原纤维增生、沉积,纤维化面积明显增加(P<0.01);心肌组织Vimentin、α-SMA蛋白表达升高(P<0.05),Jagged1、Notch1蛋白表达降低(P<0.05);血清IL-6、TNF-α、cTnI、ST2等炎症因子表达升高(P<0.05)。与模型组相比,RAS-AM各剂量组及盐酸贝那普利组一般情况均有不同程度改善;心肌超微结构病理变化有所改善,心肌纤维化有所减轻;胶原纤维面积明显减少(P<0.01);心肌组织Vimentin、α-SMA蛋白表达降低(P<0.05),Jagged1、Notch1表达升高(P<0.05);血清IL-6、TNF-α、cTnI、ST2等炎症因子表达降低(P<0.05)。结论:RAS-AM可能通过干预Jagged1/Notch1通路抑制CMT而减轻RIMF,但具体机制需要进一步深入研究。
AIM:To study the mechanism of action of radix angelica sinensis and astragalus mongholicus extract(RAS-AM)in inhibiting fibroblast transdifferentiation(CMT)and preventing radiationinduced 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 medication for 4 weeks of intervention:benazepril hydrochloride 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 expression using immunohistochemical staining techniques.ELISA was used to detect serum inflammatory 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:Compared with the blank group,the model group rats exhibited symptoms such as mental fatiguem anorexiam and loose stools;The arrangement of some myofibrils in the myocardium is disordered,with dissolution and breakage of myofibrilsm abnormal Zline structure in some partsm disordered mitochondrial arrangement,rupture of mitochondrial membranem,and rupture or disappearance of mitochondrial ridge structure in some parts.A large amount of collagen fibers proliferate and deposit in the myocardium,and the fibrotic area significantly increases(P<0.01);The expression of myocardial tissue Vimentinα-SMA protein increased(P<0.05),while the expression of Jagged1 and Notch1 proteins decreased(P<0.05);serum IL-6 and TNF-α,the expression of inflammatory factors such as cTnI and ST2 increased(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 fibers significantly decreased(P<0.01);Myocardial tissue Vimentinα-SMA protein expression decreased(P<0.05),while Jagged1 and Notch1 expression increased(P<0.05);Serum IL-6 and TNF-α,The expression of inflammatory factors such as cTnI and ST2 decreased(P<0.05).CONCLUSION:RAS-AM may alleviate RIMF by intervening in the Jagged1/Notch1 pathway to inhibit CMT.The specific mechanism still needs further investigation.