当归红芪超滤物通过抑制心脏CILP1过表达对放射性心肌纤维化的干预效应  

Interventional Effect of Angelica Sinensis Ultrafiltrate on Radiation-Induced Myocardial Fibrosis by Inhibiting the Overexpression of Cardiac CILP1

作　　者：赵晓彬 蒋虎刚 王新强 韩金晏 陈玉林 李应东 赵信科 Zhao Xiaobin;Jiang Hugang;Wang Xinqiang;Han Jinyan;Chen Yulin;Li Yingdong;Zhao Xinke(College of Integrated Traditional Chinese and Western Medicine,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China;Affiliated Hospital of Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China;Gansu Provincial Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Chronic Diseases,Lanzhou 730000,China)

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

出　　处：《世界科学技术-中医药现代化》2023年第7期2612-2620,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：甘肃省教育厅“双一流”科研重点项目(GSSYLXM-05):甘肃道地药材产业关键技术及其组方的基础与开发应用研究,负责人:李应东;甘肃省教育厅科技创新项目(2021jyjbgs-03):当归黄芪提取物抗放射性心肌纤维化药效物质基础及机制研究,负责人:李应东;甘肃省教育厅高等学校青年博士基金项目(2021QB-080):基于LncRNA(XLOC)/miR-21-5P探讨OVA在放射性心肌纤维化发生中的作用机制及当归红芪超滤物干预效应,负责人:赵信科。

摘　　要：目的明确当归红芪超滤物(RAS-RH)通过抑制心脏CILP1过表达对放射性心肌纤维化的干预效应。方法将40只SPF级Wistar雄性大鼠随机分为正常组、模型组、盐酸贝那普利组、RAS-RH组、盐酸贝那普利+RAS-RH组,采用X-ray诱导心肌细胞损伤制备心肌纤维化大鼠模型,盐酸贝那普利组给予盐酸贝那普利1.0 mg·kg^(-1)灌胃;RAS-RH组给予RAS-RH 0.6 g·kg^(-1)灌胃;盐酸贝那普利+RAS-RH组给予盐酸贝那普利1.0 mg·kg^(-1)与RAS-RH 0.6 g·kg^(-1)灌胃;模型组及正常组给予等体积生理盐水灌胃,每日1次,药物干预4周后,采用ELISA法检测各组大鼠血清NT-ProBNP、CTnⅠ、CTnT的含量;HE染色评价各组大鼠心肌组织病理变化;Masson染色评价各组大鼠心肌胶原沉积情况并计算胶原容积分数(CVF);免疫组化检测各组大鼠心肌组中α-SMA、Col-Ⅰ、Col-Ⅲ蛋白的表达水平;Western blot法检测各组大鼠心肌组织中TGF-β1、smad3、CILP1蛋白表达情况。结果与空白组比较,模型组大鼠血清中NT-ProBNP、CTnⅠ、CTnT的含量明显增加(P<0.01),心肌细胞排列紊乱,胞间存在大量纤维组织及炎性细胞浸润,心肌组织中蓝染纤维组织明显增多,心肌CVF显著增加,心肌组织α-SMA、Col-Ⅰ、Col-Ⅲ、TGF-β1、Smad3、CILP1蛋白表达升高(P<0.01);与模型组比较,盐酸贝那普利组、RAS-RH组、盐酸贝那普利+RAS-RH组大鼠血清中NT-ProBNP、cTnⅠ、CTnT含量明显降低(P<0.01),心肌细胞排列稍整齐,纤维组织及炎性细胞浸润有所改善,心肌CVF显著降低(P<0.01),心肌组织中α-SMA、Col-Ⅰ、Col-Ⅲ、TGF-β1、Smad3、CILP1蛋白表达明显降低(P<0.05)。结论当归红芪超滤物可通过抑制心脏CILP1的过表达减轻X线辐射诱导的大鼠心肌纤维化。Objective To clarify the intervention effect of Angelica Radix Astragali ultrafiltrate(RAS-RH)on radiationinduced myocardial fibrosis by inhibiting the overexpression of cardiac CILP1.Methods Forty SPF Wistar male rats were randomly divided into normal group,model group,Benazepril hydrochloride group,RAS-RH group and Benazepril hydrochloride+RAS-RH group.Cardiomyocytes were induced by X-ray.The rat model of myocardial fibrosis was prepared by injury.The benazepril hydrochloride group was given benazepril hydrochloride 1.0 mg·kg^(-1) by gavage;the RAS-RH group was given RAS-RH 0.6 g·kg^(-1) by gavage;benazepril hydrochloride was given by gavage Pril+RAS-RH group was given benazepril hydrochloride 1.0 mg·kg^(-1) and RAS-RH 0.6 g·kg^(-1) by gavage;model group and normal group were given equal volume of normal saline by gavage,once a day,After 4 weeks of drug intervention,the serum NTProBNP,CTnⅠand CTnT contents of the rats in each group were detected by ELISA method;HE staining was used to evaluate the pathological changes of myocardial tissue of the rats in each group;Masson staining was used to evaluate the myocardial collagen deposition of the rats in each group and calculated Collagen volume fraction(CVF);immunohistochemistry to detect the expression levels of α-SMA,Col-Ⅰ,Col-Ⅲ protein in myocardial tissue of rats in each group;Western blot method to detect TGF-β1 and smad3 in myocardial tissue of rats in each group,CILP1 protein expression.Results Compared with the blank group,the serum levels of NT-ProBNP,CTn Ⅰ and CTnT in the model group were significantly increased(P<0.01).Blue-stained fibrous tissue increased significantly,myocardial CVF increased significantly,and myocardial tissue α-SMA,Col-Ⅰ,Col-Ⅲ,TGF-β1,Smad3,CILP1 protein expression increased(P<0.01);Serum contents of NT-ProBNP,cTn Ⅰ and CTnT in rats in napril group,RAS-RH group and benazepril hydrochloride+RAS-RH group were significantly decreased(P<0.01).Sexual cell infiltration was improved,myocardial CVF was significantly decr

关 键 词：当归红芪超滤物 心肌纤维化 CILP1 信号通路 中医药 

分 类 号：R285.5[医药卫生—中药学]