Zhao Xuyong, Huang Bingwu, Zhang Jianhua, Xiang Wenjun, Zhu Ning
Department of Cardiology, The Wenzhou Third Clinical Institute, The Third Affiliated Hospital of Shanghai University, Wenzhou Medical University, Wenzhou People's Hospital, No. 299 Guan Road, Wenzhou, Zhejiang Province, People's Republic of China.
Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Diabetol Metab Syndr. 2023 Sep 12;15(1):186. doi: 10.1186/s13098-023-01159-x.
Heart failure is closely correlated with diabetic cardiomyopathy (DCM) and can lead to mortality. Celastrol has long been utilized for the treatment of immune and inflammatory disorders. However, whether celastrol would exert protective effects on DCM has not been determined. This work aimed to explore the protective actions of celastrol on DCM and unravel the underlying mechanisms involved.
A DCM model was constructed in mice by intraperitoneal administration of streptozotocin. ELISA and echocardiography were performed to examine myocardial injury markers and cardiac function, respectively. Morphological changes and fibrosis were assessed using H&E staining and Masson's staining. Inflammatory cytokines and fibrotic markers were detected by ELISA and RT-PCR. Endothelial nitric oxide synthase, apoptosis, and reactive oxygen species were detected by microscopic staining. Network pharmacology approaches, molecular docking analysis, ELISA, and Western blot were used for mechanism studies.
Celastrol alleviated diabetes-induced cardiac injury and remodeling. Celastrol also suppressed diabetes-induced production of inflammatory cytokines and reactive oxygen species, as well as cardiomyocyte apoptosis. The cardioprotective effects of celastrol were associated with its inhibition on the angiotensin-converting enzyme / angiotensin II / angiotensin II receptor type 1 signaling pathway.
Celastrol exhibits significant potential as an effective cardioprotective drug for DCM treatment. The underlying mechanisms can be attributed to the blockage of celastrol on the angiotensin-converting enzyme signaling pathway.
心力衰竭与糖尿病性心肌病（DCM）密切相关，可导致死亡。雷公藤红素长期以来一直用于治疗免疫和炎症性疾病。然而，雷公藤红素是否对DCM具有保护作用尚未确定。本研究旨在探讨雷公藤红素对DCM的保护作用，并揭示其潜在机制。
通过腹腔注射链脲佐菌素构建小鼠DCM模型。分别采用酶联免疫吸附测定（ELISA）和超声心动图检测心肌损伤标志物和心功能。采用苏木精-伊红（H&E）染色和Masson染色评估形态学变化和纤维化。通过ELISA和逆转录-聚合酶链反应（RT-PCR）检测炎症细胞因子和纤维化标志物。通过显微镜染色检测内皮型一氧化氮合酶、细胞凋亡和活性氧。采用网络药理学方法、分子对接分析、ELISA和蛋白质免疫印迹法进行机制研究。
雷公藤红素减轻了糖尿病诱导的心脏损伤和重塑。雷公藤红素还抑制了糖尿病诱导的炎症细胞因子和活性氧的产生，以及心肌细胞凋亡。雷公藤红素的心脏保护作用与其对血管紧张素转换酶/血管紧张素II/血管紧张素II 1型受体信号通路的抑制作用有关。
雷公藤红素作为一种有效的DCM治疗心脏保护药物具有显著潜力。其潜在机制可归因于雷公藤红素对血管紧张素转换酶信号通路的阻断作用。
