Astragaloside IV (AsIV) is an active saponin extracted from Astragalus membranaceus, which has shown cardioprotective effects in a number of experimental animals. In this study we investigated the molecular mechanisms by which AsIV attenuated the myocardial ischemia reperfusion (MI/R)-induced injury in vitro and in vivo by focusing on calcium-sensing receptor (CaSR) and extracellular signal-regulated kinase 1/2 (ERK1/2). Rat neonatal cardiac myocytes were subjected to a hypoxia/reoxygenation (H/R) procedure in vitro, which significantly decreased the cell viability, increased lactate dehydrogenase (LDH) release, induced cardiomyocyte apoptosis, and increased [Ca2+]i. H/R also increased the expression of CaSR and decreased ERK1/2 phosphorylation levels in H/R-exposed myocytes. Pretreatment with AsIV (60 μmol/L) significantly improved the cell viability and decreased LDH release, attenuated myocyte apoptosis, decreased [Ca2+]i and CaSR expression, and increased the ERK1/2 phosphorylation levels. The protective effects of AsIV against H/R injury were partially inhibited by co-treatment with a CaSR agonist, gadolinium chloride (GdCl3) or with a specific ERK1/2 inhibitor U0126. For in vivo studies, a rat MI/R model was established. Pre-administration of AsIV (80 mg/kg every day, ig) significantly decreased the myocardium infarct size, creatine kinase-MB (CK-MB) production, serum cardiac troponin (cTnI) levels, and cardiomyocyte apoptosis in the rats with MI/R injury. The therapeutic effects of AsIV were associated with the downregulation of CaSR expression and upregulation of ERK1/2 phosphorylation in myocardial tissues. In summary, astragaloside IV attenuates myocardial I/R injury via inhibition of CaSR/ERK1/2 and the related apoptotic signaling pathways.

中文翻译：

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黄芪甲苷通过抑制钙敏感受体介导的凋亡信号通路减轻大鼠心肌缺血/再灌注损伤。

黄芪甲苷 (AsIV) 是一种从黄芪中提取的活性皂苷，已在许多实验动物中显示出心脏保护作用。在这项研究中，我们通过关注钙敏感受体 (CaSR) 和细胞外信号调节激酶 1/2 (ERK1 /2）。大鼠新生心肌细胞在体外进行缺氧/复氧（H/R）程序，显着降低细胞活力，增加乳酸脱氢酶（LDH）释放，诱导心肌细胞凋亡，并增加[Ca2+]i。H/R 还增加了 CaSR 的表达并降低了暴露于 H/R 的肌细胞中的 ERK1/2 磷酸化水平。用 AsIV (60 μmol/L) 预处理可显着提高细胞活力并减少 LDH 释放，减弱心肌细胞凋亡，降低 [Ca2+]i 和 CaSR 表达，并增加 ERK1/2 磷酸化水平。AsIV 对 H/R 损伤的保护作用通过与 CaSR 激动剂、氯化钆 (GdCl3) 或特定的 ERK1/2 抑制剂 U0126 共同处理而被部分抑制。对于体内研究，建立了大鼠 MI/R 模型。预先给予 AsIV（每天 80 mg/kg，ig）可显着降低 MI 大鼠的心肌梗死面积、肌酸激酶-MB（CK-MB）的产生、血清心肌肌钙蛋白（cTnI）水平和心肌细胞凋亡。 R伤害。AsIV 的治疗作用与心肌组织中 CaSR 表达的下调和 ERK1/2 磷酸化的上调有关。