Cai Zhenhao, Sun Fengxiao, Wang Qingyan, Li Shengnan, Wang Lanlan, Li Huixin, Su Yudong, Yang Hongbo, Dong Bo
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China; Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
Int Immunopharmacol. 2025 May 27;156:114690. doi: 10.1016/j.intimp.2025.114690. Epub 2025 Apr 21.
Among the multitude of pressing global health concerns, diabetes mellitus stands out as a significant issue. An alarming consequence of this condition is diabetic cardiomyopathy (DCM), which represents a critical contributor to mortality in individuals with diabetes. Recently, research has unveiled the pivotal role that pyroptosis plays in the progression of myocardial fibrosis associated with DCM. An epimedial flavonoid monomer, Icariin (ICA), primarily sourced from Epimedium genus plants, has shown a safeguarding influence on cardiac health through various means, encompassing anti-inflammatory actions and its capacity against oxidative stress. Our research endeavor focuses on elucidating the beneficial impacts alongside the underlying physiological processes triggered by ICA within the context of DCM. An animal model representative of DCM was developed through intraperitoneal administration of streptozotocin (STZ). In parallel, in vitro experiments utilized H9C2 cardiomyocytes to mimic hyperglycemic environments relevant to disease states. In vivo experiments found that ICA improved cardiac function, alleviated myocardial fibrosis, and reduced NLRP3-mediated pyroptosis in heart tissue of DCM mice. Under in vitro settings characterized by elevated glucose concentrations, there was a notable elevation in both NLRP3 pyroptosis-associated proteins and oxidative stress markers within the heart muscle cells. ICA treatment attenuated pyroptosis and oxidative stress caused by high glucose in cardiomyocytes. Further studies revealed that when treated with an AMPK inhibitor, the shielding benefits conferred by ICA on cardiomyocytes were negated, suggesting that the regulatory effects of ICA on cardiomyocyte pyroptosis may be achieved through the AMPK-NLRP3 pathway. In conclusion, ICA exerts protective effects in DCM by inhibiting cardiomyocyte pyroptosis, alleviating myocardial fibrosis, and improving cardiac function via the AMPK-NLRP3 pathway.
在众多紧迫的全球健康问题中，糖尿病是一个重大问题。这种疾病的一个惊人后果是糖尿病性心肌病（DCM），它是糖尿病患者死亡的一个关键因素。最近，研究揭示了细胞焦亡在与DCM相关的心肌纤维化进展中所起的关键作用。一种主要来源于淫羊藿属植物的淫羊藿黄酮单体，淫羊藿苷（ICA），已通过多种方式对心脏健康显示出保护作用，包括抗炎作用及其对抗氧化应激的能力。我们的研究致力于阐明ICA在DCM背景下引发的有益影响以及潜在的生理过程。通过腹腔注射链脲佐菌素（STZ）建立了一个代表DCM的动物模型。同时，体外实验利用H9C2心肌细胞模拟与疾病状态相关的高血糖环境。体内实验发现，ICA改善了DCM小鼠心脏组织的心脏功能，减轻了心肌纤维化，并减少了NLRP3介导的细胞焦亡。在以高葡萄糖浓度为特征的体外环境中，心肌细胞内NLRP3细胞焦亡相关蛋白和氧化应激标志物均显著升高。ICA处理减轻了高糖引起的心肌细胞焦亡和氧化应激。进一步研究表明，当用AMPK抑制剂处理时，ICA赋予心肌细胞的保护作用被抵消，这表明ICA对心肌细胞焦亡的调节作用可能是通过AMPK-NLRP3途径实现的。总之，ICA通过抑制心肌细胞焦亡、减轻心肌纤维化并通过AMPK-NLRP3途径改善心脏功能，在DCM中发挥保护作用。
