| 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） |
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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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