Abstract Context Heart failure is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used in the treatment of cardiovascular diseases. Objective To elucidate the antioxidative mechanism of ASI in a rat model of left coronary artery ligation. Materials and methods Left coronary artery of Sprague–Dawley rats was ligated to establish the model of heart failure, and then vehicle (saline) or ASI (1 mg/kg/day) was orally administered to the rats (n = 15) for 6 weeks. Echocardiography was used to evaluate the cardiac function. Myocardial infarct size was measured by triphenyltetrazolium chloride staining. Oxidative stress in the ventricular myocardium was determined. Molecular mechanisms were investigated by Western blot and chromatin immunoprecipitation. Results ASI improved the cardiac function, especially ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%), and reduced the infarct size of left ventricle (20.69 ± 2.98% vs. 39.11 ± 3.97%). ASI maintained the levels of glutathione, catalase and superoxide dismutase and prevented the leakage of creatine kinase. In addition, ASI induced the protein expression of Nrf2 (1.97-fold) and HO-1 (2.79-fold), while reduced that of Keap-1 (0.77-fold) in the ventricular myocardium. In H9c2 cells, a rat cardiomyocyte cell line, ASI induced the translocation of Nrf2 from cytoplasm to nucleus, followed by transcriptional activation of NQO-1 (8.27-fold), SOD-2 (3.27-fold) and Txn-1 (9.83-fold) genes. Discussion and conclusions ASI prevented heart failure by counteracting oxidative stress through the Nrf2/HO-1 pathway. Application in clinical practice warrants further investigation.

中文翻译：

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Nrf2在黄芪甲苷介导的心力衰竭抗氧化保护中的作用

摘要 心力衰竭是世界范围内最严重的疾病之一。黄芪甲苷（ASI）广泛用于治疗心血管疾病。目的阐明ASI在大鼠左冠状动脉结扎模型中的抗氧化机制。材料与方法 结扎 Sprague-Dawley 大鼠左冠状动脉建立心力衰竭模型，然后给大鼠（n = 15）口服赋形剂（生理盐水）或 ASI（1 mg/kg/day）6周。超声心动图用于评估心脏功能。通过三苯基四唑氯化物染色测量心肌梗塞大小。测定心室心肌中的氧化应激。通过蛋白质印迹和染色质免疫沉淀研究分子机制。结果 ASI 改善了心脏功能，尤其是射血分数 (75.27 ± 5.75% vs. 36.26 ± 4.14%) 和缩短分数 (45.39 ± 3.66% vs. 17.88 ± 1.32%)，并减少了左心室的梗塞面积 (20.69 ± 2.98% vs. 1% ±39 ± 39%) ）。ASI 维持谷胱甘肽、过氧化氢酶和超氧化物歧化酶的水平并防止肌酸激酶的泄漏。此外，ASI 诱导了 Nrf2（1.97 倍）和 HO-1（2.79 倍）的蛋白表达，同时降低了心室心肌中 Keap-1（0.77 倍）的蛋白表达。在大鼠心肌细胞系 H9c2 细胞中，ASI 诱导 Nrf2 从细胞质到细胞核的易位，随后 NQO-1（8.27 倍）、SOD-2（3.27 倍）和 Txn-1（9.83-倍）的转录激活折叠）基因。讨论和结论 ASI 通过 Nrf2/HO-1 通路抵抗氧化应激来预防心力衰竭。