Abstract：
Diabetic cardiomyopathy (DCM) is characterized by oxidative damage and inflammatory responses. Myeloid differentiation protein 1 (MD1) exhibits antioxidant and anti-inflammatory properties. However, the specific role of MD1 in DCM has yet to be elucidated. This study aims to investigate the role of MD1 in DCM and to elucidate the underlying mechanisms. We utilized a gain-of-function approach to explore the involvement of MD1 in DCM. Diabetes was induced in MD1-transgenic (MD1-TG) mice and their wild-type (WT) counterparts via streptozotocin (STZ) injection. Additionally, a diabetes cell model was established using H9c2 cells exposed to high glucose levels. We conducted comprehensive evaluations, including pathological analyses, echocardiography, electrocardiography, and molecular assessments, to elucidate the underlying mechanisms of MD1 in DCM. Notably, MD1 expression was reduced in the hearts of STZ-induced diabetic mice. Overexpression of MD1 significantly improved cardiac function and markedly inhibited ventricular pathological hypertrophy and fibrosis in these mice. Furthermore, MD1 overexpression resulted in a substantial decrease in myocardial reactive oxygen species (ROS) accumulation, mitigating myocardial oxidative stress and reducing the levels of inflammation-related markers such as IL-1β, IL-6, and TNF-α. Mechanistically, MD1 overexpression inhibited the activation of the TLR4/STAT3 signaling pathway, as demonstrated in both in vivo and in vitro experiments. The overexpression of MD1 significantly impeded pathological cardiac remodeling and improved cardiac function in STZ-induced diabetic mice. This effect was primarily attributed to a reduction in ROS accumulation and mitigation of myocardial oxidative stress and inflammation, facilitated by the inhibition of the TLR4/STAT3 signaling pathway.
摘要：
糖尿病心肌病（DCM）的特征是氧化损伤和炎症反应。骨髓分化蛋白1（MD1）具有抗氧化和抗炎特性。然而,MD1在DCM中的具体作用尚未阐明。本研究旨在探讨MD1在DCM中的作用及其机制。我们利用功能获得方法来探索MD1在DCM中的参与。通过链脲佐菌素（STZ）注射在MD1转基因（MD1-TG）小鼠及其野生型（WT）对应物中诱导糖尿病。此外,使用暴露于高糖水平的H9c2细胞建立糖尿病细胞模型.我们进行了全面的评估，包括病理分析，超声心动图,心电图,和分子评估，阐明MD1在DCM中的潜在机制。值得注意的是,在STZ诱导的糖尿病小鼠的心脏中MD1表达降低。MD1的过表达可显着改善这些小鼠的心功能，并显着抑制心室病理性肥大和纤维化。此外，MD1过表达导致心肌活性氧（ROS）积累大幅减少，减轻心肌氧化应激和降低炎症相关标志物如IL-1β的水平，IL-6和TNF-α。机械上,MD1过表达抑制TLR4/STAT3信号通路的激活,正如在体内和体外实验中所证明的那样。在STZ诱导的糖尿病小鼠中，MD1的过表达显着阻碍了病理性心脏重塑并改善了心脏功能。这种效应主要归因于ROS积累的减少和心肌氧化应激和炎症的缓解。通过抑制TLR4/STAT3信号通路来促进。
