强心方（QXF）是一种著名的中草药，在亚洲被广泛用于治疗心血管疾病数千年，但其作用机制仍不清楚。本研究旨在说明强心方能否通过促进转录因子Krüppel样因子5（KLF5）的激活诱导葡萄糖代谢和抑制心肌细胞自噬。我们使用多柔比星构建H9C2心肌细胞损伤模型，并使用RNA测序数据分析检测了强心方的机制。在体内实验中，将C57 BL / 6小鼠注射多柔比星（每6天4毫克/千克，共30天），构建CHF小鼠模型，并随机分为正常对照组、Dox组和Dox + QXF组（2.12克/千克/天，4.24克/千克/天，共30天）。使用超声心动图、血清生化指标BNP、cTnl和组织病理学检查涉及HE染色、Tunel染色和免疫荧光共定位分析QXF的治疗机制。我们验证了强心方可以通过增强葡萄糖代谢和减少细胞自噬来逆转心肌细胞死亡，从而改善CHF。我们发现，强心方通过促进转录因子Krüppel-like factor 5（KLF5）的激活来诱导心肌细胞的葡萄糖代谢和抑制自噬。此外，我们确定KLF5增加了己糖激酶2（HK2）和B细胞CLL /淋巴瘤2（BCL2）基因的启动子活性，进一步增强了心肌细胞的葡萄糖代谢和抑制自噬。我们强调了KLF5介导的信号通路在CHF治疗中的重要性，这表明它们参与了多柔比星诱导心肌细胞损伤模型中的葡萄糖代谢和自噬，并表明强心方可用作治疗CHF的新型靶向疗法。与以往研究相比，我们从能量代谢的角度为多柔比星诱导的CHF治疗提供了新思路。 版权所有©2023 The Author(s). 由Elsevier GmbH出版。保留所有权利。

Qiangxin recipe (QXF) is a well-known Chinese herbal medicine commonly used in Asia for thousands of years to treat cardiovascular diseases, but its underlying mechanism remains unclear.This study aimed to illustrate whether Qiangxin Recipe (QXF) induce glucose metabolism and inhibit cardiomyocyte apoptosis by promoting the activation of the transcription factor Krüppel like factor 5 (KLF5).In vitro experiments, we constructed an H9C2 cardiomyocyte injury model using doxorubicin and used RNA-seq data analysis to detect the mechanism of QXF. In in vivo experiments, C57 BL/6 mice injected with doxorubicin (4 mg/kg every 6 days, for 30 days) to construct a CHF mouse model and randomly divided into to the normal control group, Dox group and Dox+QXF group (2.12 g/kg/day, 4.24 g/kg/day, for 30 days). Using Echocardiography, serum biochemical indices BNP, cTnl; and histopathological tests involving HE staining, Tunel staining and Immuno-dual fluorescence colocalization to analyze the therapeutic mechanism of QXF.We verified that the Qiangxin recipe could reverse cardiomyocyte dying through enhancing glucose metabolism and reducing apoptosis to improve CHF. Mechanistically, we discovered that the Qiangxin recipe promoted the activation of transcription factor Krüppel-like factor 5 (KLF5) to induce glucose metabolism and inhibit apoptosis in cardiomyocytes. Further, we identified that KLF5 increased the promoter activity of hexokinase 2 (HK2) and B-cell CLL/lymphoma 2 (BCL2) genes, which further enhanced glucose metabolism and inhibited apoptosis of cardiomyocytes.We highlighted the importance of KLF5-mediated signaling pathways in the treatment of CHF as shown by their participation in glucose metabolism and apoptosis in a doxorubicin-induced model of cardiomyocyte injury, as well as show that Qiangxin recipe can be used as a novel targeted therapy for the treatment of CHF. Compared with previous studies, we provide new ideas for the treatment of Doxorubicin-induced CHF from the perspective of energy metabolism.Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.