Dapagliflozin (DPG) 是一种钠-葡萄糖协同转运蛋白 2 抑制剂，用于治疗糖尿病。在本研究中，我们旨在研究 DPG 对通过内质网 (ER) 应激和自噬引起的全身炎症引起的心脏毒性的影响。创建了四组，每组 32 只 Wistar Albino 大鼠： 对照组（1 ml 口服生理盐水，连续五天）和第 5 天腹腔注射生理盐水）、LPS（口服 1 ml 生理盐水，连续 5 天，第 5 天腹腔注射 5 mg/kg LPS）、LPS  DPG（口服 10 mg/kg DPG，连续 5 天，5 mg/kg） kg LPS（第 5 天腹腔注射）和 DPG（口服 10 mg/kg DPG，连续 5 天；第 5 天腹腔注射 5 mg/kg SF）。对心脏和主动脉组织进行组织病理学和免疫组织化学分析。通过 RT-qPCR 评估心脏组织中的 ER 应激和自噬基因标记。采用分光光度法分析心脏组织氧化应激和血清心肌酶。 LPS组心脏和主动脉组织肿瘤坏死因子-α（TNF-α）和Caspase-3（Cas-3）表达增加，并伴有轻度充血、轻微炎性细胞浸润和心肌细胞损伤。心脏组织还表现出基因表达增加，包括结合免疫球蛋白 (BiP/GRP78)、蛋白激酶 RNA 样 ER 激酶 (PERK)、肌醇需求酶 1 (IRE-1)、激活转录因子 4 (ATF-4) 、激活转录因子 4 (ATF6)、C/EBP 同源蛋白 (CHOP) 和 BECLIN 1。此外，根据生化分析，血液组织中的肌酸激酶-MB (CK-MB) 和乳酸脱氢酶 (LDH) 水平显着升高。通过 DPG 治疗，所有这些发现都得到了逆转。总之，DPG 通过调节 ER 应激和自噬途径，利用其抗氧化和抗炎特性，防止全身炎症的心脏毒性作用。© 2024。作者，独家Springer Nature B.V. 的许可

Dapagliflozin (DPG) is a sodium-glucose cotransporter-2 inhibitor and is used in the treatment of diabetes. In this study, we aimed to investigate the effect of DPG on cardiotoxicity caused by systemic inflammation via endoplasmic reticulum (ER) stress and autophagy.Four groups of thirty-two Wistar Albino rats were created: Control (1 ml oral physiological saline for five days and intraperitoneal saline on the 5th day), LPS (1 ml oral physiological saline for five days and intraperitoneal 5 mg/kg of LPS on the 5th day), LPS + DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of LPS intraperitoneally on the 5th day), and DPG (10 mg/kg of DPG orally for five days and 5 mg/kg of SF intraperitoneally on the 5th day). Histopathological and immunohistochemical analyses were performed on heart and aorta tissues. ER stress and autophagy gene markers in heart tissues were evaluated by RT-qPCR. Oxidative stress in heart tissues and serum cardiac enzymes were analyzed by spectrophotometric method. The heart and aortic tissues of the LPS group showed increased expressions of Tumor Necrosis Factor-α (TNF-α) and Caspase-3 (Cas-3), along with mild hyperemia, slight inflammatory cell infiltrations, and myocardial cell damage. The heart tissues also showed genetically increased expressions of include binding immunoglobulin protein (BiP/ GRP78), protein kinase RNA-like ER Kinase (PERK), inositol-requiring enzyme 1 (IRE-1), activating transcription factors 4 (ATF-4), activating transcription factors 4 (ATF6), C/EBP homologous protein (CHOP), and BECLIN 1. Furthermore, Creatine kinase-MB (CK-MB) and Lactate dehydrogenase (LDH) levels in blood tissue significantly increased, according to biochemical analysis. With DPG therapy, all of these findings were reversed.In conclusion, DPG protects against the cardiotoxic effect of systemic inflammation with its antioxidant and anti-inflammatory properties by regulating ER stress and autophagy pathways.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.