Role of Oxidative Stress in Diabetic Cardiomyopathy.
Role of Oxidative Stress in Diabetic Cardiomyopathy.
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氧化应激在糖尿病心肌病中的作用
DOI：
10.3390/antiox11040784
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发表时间：
2022-04-15
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影响因子：
--
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2型糖尿病是一种氧化还原疾病。氧化应激和慢性炎症会引起代谢稳态设定点的转变，导致葡萄糖不耐受。几种糖尿病特有的机制会导致心脏显着的氧化应激，从而导致糖尿病心肌病的发展。糖尿病受试者中线粒体活性氧的过量产生不仅是由微脉管系统中的细胞内高血糖引起的，也是心肌细胞中脂肪氧化和脂毒性增加的结果。线粒体过量产生超氧阴离子自由基，通过抑制 3-磷酸甘油醛脱氢酶，诱导多元醇途径通量增加、晚期糖基化终产物 (AGE) 形成增加和 AGE 受体 (RAGE) 激活、蛋白激酶 C 同工型激活和己糖胺途径通量增加。这些途径不仅直接导致糖尿病性心肌病，而且本身也是额外活性氧的来源。活性氧和氧化应激不仅通过蛋白质氧化、脂质过氧化、DNA 损伤和 microRNA 的氧化变化，而且还通过应激敏感途径和氧化还原调节的激活，导致细胞功能障碍和细胞损伤。对糖尿病心肌病动物模型的研究一致表明，主要抗氧化酶表达的增加可减轻心肌病理并改善心脏功能。
Type 2 diabetes is a redox disease. Oxidative stress and chronic inflammation induce a switch of metabolic homeostatic set points, leading to glucose intolerance. Several diabetes-specific mechanisms contribute to prominent oxidative distress in the heart, resulting in the development of diabetic cardiomyopathy. Mitochondrial overproduction of reactive oxygen species in diabetic subjects is not only caused by intracellular hyperglycemia in the microvasculature but is also the result of increased fatty oxidation and lipotoxicity in cardiomyocytes. Mitochondrial overproduction of superoxide anion radicals induces, via inhibition of glyceraldehyde 3-phosphate dehydrogenase, an increased polyol pathway flux, increased formation of advanced glycation end-products (AGE) and activation of the receptor for AGE (RAGE), activation of protein kinase C isoforms, and an increased hexosamine pathway flux. These pathways not only directly contribute to diabetic cardiomyopathy but are themselves a source of additional reactive oxygen species. Reactive oxygen species and oxidative distress lead to cell dysfunction and cellular injury not only via protein oxidation, lipid peroxidation, DNA damage, and oxidative changes in microRNAs but also via activation of stress-sensitive pathways and redox regulation. Investigations in animal models of diabetic cardiomyopathy have consistently demonstrated that increased expression of the primary antioxidant enzymes attenuates myocardial pathology and improves cardiac function.
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