糖尿病/肥胖相关的炎症,心肌细胞死亡及心肌病(英文)

Diabetes/obesity-related inflammation, cardiac cell death and cardiomyopathy

糖尿病心肌病( DCM)是糖尿病引发的一种慢性心肌病理改变。在这一慢性病理过程中,急性心肌反应如心肌细胞死亡起关键性的启动作用。除了高血糖,炎症反应也是引起糖尿病性心肌病心肌细胞死亡的一个重要因素。研究证实,糖尿病或肥胖经常可导致全身包括心脏中的肿瘤坏死因子-α( TGF-α) ,白介素-18和血小板激活抑制因子-1( PAI-1)的升高。这些细胞因子引起心肌细胞死亡的机制主要是与氧化和/或氮化损伤相关。金属硫蛋白做为一个有效的抗氧化剂,可以保护心肌免受氧化应激损伤以及细胞因子引发的心肌细胞死亡,从而有效地防止DCM的发生。应用特异性的超氧化抑制剂可以完全阻断细胞因子导致的心肌细胞死亡,所以抑制氧化应激可以有效防止心肌死亡。因此,糖尿病诱发的炎症因子通过氧化应激反应所诱发的心肌细胞死亡是糖尿病心肌病( DCM)发生发展中的重要始动因子。

Pathogenesis of diabetic cardiomyopathy （DCM） is a complicate and chronic process that is secondaryto acute cardiac responses to diabetes. One of the acute responses is cardiac cell death that plays a critical role in the initiation and development of DCM. Besides hyperglycemia, inflammatory response in the diabetic heart is also a major.cause for cardiac cell death. Diabetes or obesity often causes systemic and cardiac increases in tumor necrosis factor-alpha, interleukin-18 and plasminogen activator inhibitor-1. However, how these cytokines cause cardiac cell death remains unclear. It has been considered to relate to oxidative and/or nitrosative stress. We have demonstrated that metallothionein as a potent antioxidant dative damage and cell death caused by these cytokines, the inhibition of oxidative stress and damage to the preven or stress protein significantly protected the heart from oxileading to effective prevention of DCM. The direct link of tion of cardiac cell death was defined by addition of superoxide or peroxynitrite specific inhibitor to completely prevent cytokine-induced cardiac cell death. Cardiac cell death is induced by the inflammatory cytokines that is increased in response to diabetes. Inflammatory cytokineinducedcardiac cell death is mediated by oxidative stress and is also the major initiator for DCM development.