糖尿病性心肌病(DCM)是全球范围内的主要死亡原因,并且发现氧化应激在该病症的病理生理学中起重要作用。已知自由基和抗氧化防御之间的不平衡与细胞功能障碍有关。导致各种类型的心脏病的发展。核因子-红系-2相关因子2(NRF2)是一种转录因子,可控制各种抗氧化基因和其他II期细胞保护性解毒酶的基础和诱导型表达水平,在心脏系统中普遍表达。Kelch样ECH相关蛋白1(Keap1)是NRF2的主要细胞内调节因子。新出现的证据表明NRF2是通过抑制氧化应激的心脏稳态的关键调节剂。发现NRF2的激活可以增强特定的内源性抗氧化防御因子,其中之一是抗氧化反应元件(ARE),随后被证明可以解毒并抵消与氧化应激相关的DCM。NRF2信号通路与各类心脏病的发生发展密切相关,包括缺血性心脏病,心力衰竭,心肌梗塞,心房颤动和心肌炎。因此,据推测,靶向该途径的药物可能被开发来抑制NRF2信号的激活,从而预防DCM的发生,有效治疗该病。
Diabetic cardiomyopathy (DCM) is the leading cause of death worldwide, and oxidative stress was discovered to serve an important role in the pathophysiology of the condition. An imbalance between free radicals and antioxidant defenses is known to be associated with cellular dysfunction, leading to the development of various types of cardiac disease. Nuclear factor-erythroid-2-related factor 2 (NRF2) is a transcription factor that controls the basal and inducible expression levels of various antioxidant genes and other cytoprotective phase II detoxifying enzymes, which are ubiquitously expressed in the cardiac system. Kelch-like ECH-associated protein 1 (Keap1) serves as the main intracellular regulator of NRF2. Emerging evidence has revealed that NRF2 is a critical regulator of cardiac homeostasis via the suppression of oxidative stress. The activation of NRF2 was discovered to enhance specific endogenous antioxidant defense factors, one of which is antioxidant response element (ARE), which was subsequently illustrated to detoxify and counteract oxidative stress-associated DCM. The NRF2 signaling pathway is closely associated with the development of various types of cardiac disease, including ischemic heart disease, heart failure, myocardial infarction, atrial fibrillation and myocarditis. Therefore, it is hypothesized that drugs targeting this pathway may be developed to inhibit the activation of NRF2 signaling, thereby preventing the occurrence of DCM and effectively treating the disease.