This study aimed to investigate whether inhibition of endoplasmic reticulum stress (ERS) mediated the ameliorative effect of apelin on acute heart failure (AHF). Rabbit model of AHF was induced by sodium pentobarbital. Cardiac dysfunction and injury were detected in the rabbit models of AHF, including impaired hemodynamic parameters and increased levels of CK-MB and cTnI. Apelin treatment dramatically improved cardiac impairment caused by AHF. ERS, indexed by increased GRP78, CHOP, and cleaved-caspase12 protein levels, was simultaneously attenuated by apelin. Apelin also could ameliorate increased protein levels of cleaved-caspase3 and Bax, and improved decreased protein levels of Bcl-2. Two common ERS stimulators, tunicamycin (Tm) and dithiothreitol (DTT) blocked the ameliorative effect of apelin on AHF. Phosphorylated Akt levels increased after apelin treatment in the rabbit models of AHF. The Akt signaling inhibitors wortmannin and LY294002 could block the cardioprotective effect of apelin, which could be relieved by ERS inhibitor 4-phenyl butyric acid (4-PBA). The aforementioned beneficial effects of apelin could all be blocked by APJ receptor antagonist F13A. 4-PBA and SC79, an Akt activator, can restore the ameliorative effect of apelin on AHF blocked by F13A. Apelin treatment dramatically ameliorated cardiac impairment caused by AHF, which might be mediated by APJ/Akt/ERS signaling pathway. These results will shed new light on AHF therapy.

本研究旨在探讨抑制内质网应激 (ERS) 是否介导了 apelin 对急性心力衰竭 (AHF) 的改善作用。戊巴比妥钠诱导AHF兔模型。在 AHF 兔模型中检测到心脏功能障碍和损伤，包括血流动力学参数受损和 CK-MB 和 cTnI 水平升高。Apelin 治疗显着改善了 AHF 引起的心脏损伤。ERS，由增加的 GRP78、CHOP 和 cleaved-caspase12 蛋白水平指示，同时被 apelin 减弱。Apelin 还可以改善 cleaved-caspase3 和 Bax 的蛋白质水平增加，并改善 Bcl-2 的蛋白质水平下降。两种常见的 ERS ​​刺激剂，衣霉素 (Tm) 和二硫苏糖醇 (DTT) 可阻断 apelin 对 AHF 的改善作用。在 AHF 兔模型中，apelin 治疗后磷酸化 Akt 水平增加。Akt 信号抑制剂渥曼青霉素和 LY294002 可以阻断 apelin 的心脏保护作用，ERS 抑制剂 4-苯基丁酸 (4-PBA) 可以缓解这种作用。APJ受体拮抗剂F13A可以阻断apelin的上述有益作用。4-PBA 和 SC79（一种 Akt 激活剂）可以恢复 apelin 对 F13A 阻断的 AHF 的改善作用。Apelin 治疗显着改善了 AHF 引起的心脏损伤，这可能是由 APJ/Akt/ERS 信号通路介导的。这些结果将为 AHF 治疗提供新的线索。这可以通过 ERS ​​抑制剂 4-苯基丁酸 (4-PBA) 缓解。APJ受体拮抗剂F13A可以阻断apelin的上述有益作用。4-PBA 和 SC79（一种 Akt 激活剂）可以恢复 apelin 对 F13A 阻断的 AHF 的改善作用。Apelin 治疗显着改善了 AHF 引起的心脏损伤，这可能是由 APJ/Akt/ERS 信号通路介导的。这些结果将为 AHF 治疗提供新的线索。这可以通过 ERS ​​抑制剂 4-苯基丁酸 (4-PBA) 缓解。APJ受体拮抗剂F13A可以阻断apelin的上述有益作用。4-PBA 和 SC79（一种 Akt 激活剂）可以恢复 apelin 对 F13A 阻断的 AHF 的改善作用。Apelin 治疗显着改善了 AHF 引起的心脏损伤，这可能是由 APJ/Akt/ERS 信号通路介导的。这些结果将为 AHF 治疗提供新的线索。