黄芪甲苷对阿霉素诱导的扩张型心肌病大鼠心肌纤维化和Th17细胞分化的影响  

Effects of Astragaloside Ⅳon Myocardial Fibrosis and Th17 Cell Differentiation in Rats with Adriamycin Induced Dilated Cardiomyopathy

作　　者：薛松妍 董怡 王冕 王丹 李森 马静 XUE Song-yan;DONG Yi;WANG Mian;WANG Dan;LI Sen;MA Jing(Department of Traditional Chinese Medicine,The First Affiliated Hospital of Air Force Medical University,Xi'an,Shaanxi,710032,China)

机构地区：[1]空军军医大学第一附属医院中医科,陕西西安710032

出　　处：《现代生物医学进展》2024年第12期2207-2213,2268,共8页Progress in Modern Biomedicine

基　　金：陕西省中医药管理局科研立项课题(2021-ZZ-JC015);西安交通大学机械制造系统工程国家重点实验室开放课题(sklms2021013)。

摘　　要：目的:探究黄芪甲苷(AS-Ⅳ)对阿霉素诱导的扩张型心肌病(DCM)大鼠心肌纤维化和Th17细胞分化的影响。方法:采用剂量为2.5 mg/kg的阿霉素腹腔注射诱导构建DCM大鼠模型,将DCM大鼠分为模型组、黄芪甲苷低剂量组(低AS-Ⅳ组)、黄芪甲苷中剂量组(中AS-Ⅳ组)和黄芪甲苷高剂量组(高AS-Ⅳ组),每组10只;另设置10只健康SD大鼠为对照组。低AS-Ⅳ组、中AS-Ⅳ组和高AS-Ⅳ组大鼠每日灌胃给予剂量为20 mg/kg、40 mg/kg和80 mg/kg的AS-Ⅳ,每日1次,共给药6周;对照组和模型组大鼠同时给予等体积生理盐水灌胃。给药结束后,超声检测各组大鼠心脏功能指数:左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)和左室射血分数(LVEF)。采用苏木精-伊红(HE)染色和Masson染色检测大鼠心肌组织病理变化,流式细胞术检测大鼠脾脏组织Th17细胞水平,ELISA法检测大鼠血清中IL-17、IL-21和TNF-α水平,qRT-PCR检测大鼠心肌组织RORγt和FoxP3基因表达水平,Western blot检测大鼠心肌组织α-SMA、collagenⅠ、TGF-β1、RORγt和FoxP3蛋白表达水平。结果:HE和Masson染色结果显示,模型组大鼠心肌组织出现炎性细胞浸润,细胞肥大,间质组织中蓝色染色胶原沉积量增加。与模型组比较,低AS-Ⅳ组、中AS-Ⅳ组和高AS-Ⅳ组大鼠心肌组织中炎性细胞浸润和细胞肥大情况逐渐缓解,胶原沉积量减少。与对照组比较,模型组大鼠LVESD和LVEDD指标均升高(P<0.05),LVEF指标降低(P<0.05);心肌组织α-SMA、collagenⅠ、TGF-β1和RORγt水平均升高(P<0.05),FoxP3水平降低(P<0.05);脾脏组织Th17细胞比例升高(P<0.05);血清中IL-17、IL-21和TNF-α水平均升高(P<0.05)。与模型组比较,低AS-Ⅳ组、中AS-Ⅳ组和高AS-Ⅳ组大鼠LVESD和LVEDD指标均降低(P<0.05),LVEF指标升高(P<0.05);心肌组织α-SMA、collagenⅠ、TGF-β1和RORγt水平均降低(P<0.05),FoxP3水平升高(P<0.05);脾脏组织Th17细胞比例均降低(P<0.05);血清中IL-17、Objective:To investigate the effects of astragaloside IV(AS-Ⅳ)on myocardial fibrosis and Th17 cell differentiation in rats with adriamycin induced dilated cardiomyopathy(DCM).Methods:The model of DCM rats were established by intraperitoneal injection of adriamycin at the dose of 2.5 mg/kg,and the DCM rats were divided into model group,low AS-Ⅳgroup,medium AS-Ⅳgroup and high AS-Ⅳgroup,with 10 rats in each group.In addition,10 healthy SD rats were set as control group.The rats in low AS-Ⅳgroup,medium AS-Ⅳgroup and high AS-Ⅳgroup were given AS-Ⅳat doses of 20 mg/kg,40 mg/kg and 80 mg/kg once a day for a total of 6 weeks.Rats in control group and model group were simultaneously given equal volume normal saline intragastric administration.After administration,the cardiac function index included left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD)and left ventricular ejection fraction(LVEF)were detected by ultrasound.The pathological changes of myocardial tissue were detected by Hematoxylin-eosin(HE)and Masson staining.The level of Th17 cells in spleen tissue of rats were detected by flow cytometry.The levels of IL-17,IL-21 and TNF-αin serum were detected by ELISA.The mRNA expression levels of RORγt and FoxP3 in rat myocardial tissue were detected by qRT-PCR,and the protein expressions ofα-SMA,collagen I,TGF-β1,RORγt and FoxP3 in rat myocardial tissue were detected by Western blot.Results:The results of HE and Masson staining showed that inflammatory cell infiltra tion and cell hypertrophy occurred in the myocardium of the model group, and blue-stained collagen deposition increased in the interstitialtissue. Compared with model group, inflammatory cell infiltration and cell hypertrophy in myocardium of rats in low AS-Ⅳ group,medium AS-Ⅳ group and high AS-Ⅳ group were gradually relieved, and the amount of collagen deposition was reduced. Comparedwith control group, LVESD and LVEDD indexes of model group were increased(P<0.05), while LVEF indexes were dec

关 键 词：黄芪甲苷 扩张型心肌病 心肌纤维化 TH17细胞 分化 

分 类 号：R-33[医药卫生] R542.2