文章摘要
薛松妍,董 怡,王 冕,王 丹,李 森,马 静.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[J].,2024,(12):2207-2213
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 Ⅳ on Myocardial Fibrosis and Th17 Cell Differentiation in Rats with Adriamycin Induced Dilated Cardiomyopathy
投稿时间:2024-03-01  修订日期:2024-03-15
DOI:10.13241/j.cnki.pmb.2024.12.002
中文关键词: 黄芪甲苷  扩张型心肌病  心肌纤维化  Th17细胞  分化
英文关键词: Astragaloside Ⅳ (AS-Ⅳ)  Dilated cardiomyopathy (DCM)  Myocardial fibrosis  Th17 cell  Differentiation
基金项目: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)
作者单位E-mail
薛松妍 空军军医大学第一附属医院中医科 陕西 西安 710032 XueSoYa20JD@163.com 
董 怡 空军军医大学第一附属医院中医科 陕西 西安 710032  
王 冕 空军军医大学第一附属医院中医科 陕西 西安 710032  
王 丹 空军军医大学第一附属医院中医科 陕西 西安 710032  
李 森 空军军医大学第一附属医院中医科 陕西 西安 710032  
马 静 空军军医大学第一附属医院中医科 陕西 西安 710032  
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中文摘要:
      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、collagen Ⅰ、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、collagen Ⅰ、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、IL-21和TNF-α水平均降低(P<0.05)。结论:AS-Ⅳ对阿霉素诱导的DCM大鼠具有良好的治疗效果,其机制可能与抗心肌组织纤维化和抑制Th17细胞分化相关。
英文摘要:
      ABSTRACT 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-Ⅳ group, medium AS-Ⅳ group and high AS-Ⅳ group, with 10 rats in each group. In addition, 10 healthy SD rats were set as control group. The rats in low AS-Ⅳ group, medium AS-Ⅳ group and high AS-Ⅳ group were given AS-Ⅳ at 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-α in 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 of α-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 infiltration and cell hypertrophy occurred in the myocardium of the model group, and blue-stained collagen deposition increased in the interstitial tissue. 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. Compared with control group, LVESD and LVEDD indexes of model group were increased(P<0.05), while LVEF indexes were decreased (P<0.05). The levels of α-SMA, collagen Ⅰ, TGF-β1 and RORγt in myocardial tissue were increased (P<0.05), while FoxP3 level was decreased (P<0.05). The proportion of Th17 cells in spleen tissue was increased(P<0.05). The levels of IL-17, IL-21 and TNF-α in serum were increased (P<0.05). Compared with control group, LVESD and LVEDD indexes of model group were decreased (P<0.05), while LVEF indexes were increased(P<0.05). The levels of α-SMA, collagen Ⅰ, TGF-β1 and RORγt in myocardial tissue were decreased(P<0.05), while FoxP3 level was increased(P<0.05). The proportion of Th17 cells in spleen tissue was decreased (P<0.05). The levels of IL-17, IL-21 and TNF-α in serum were decreased(P<0.05). Conclusion: AS-Ⅳ showed good therapeutic effect on DCM rats induced by adriamycin, the mechanism of which may be related to anti-myocardial fibrosis and inhibition of Th17 cell differentiation.
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