Dhalla N S, Liu X, Panagia V, Takeda N
St. Boniface General Hospital Research Centre, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Cardiovasc Res. 1998 Nov;40(2):239-47. doi: 10.1016/s0008-6363(98)00186-2.
Heart dysfunction in chronic diabetes has been observed to be associated with depressed myofibrillar adenosine triphosphatase activities as well as abnormalities in the sarcoplasmic reticular and sarcolemmal calcium transport processes. The evidence has been presented to show that alterations in the expression of myosin isozymes and regulatory proteins as well as myosin phosphorylation contribute to the development of myofibrillar remodeling in the diabetic heart. Defects in sarcoplasmic reticular and sarcolemmal calcium transport appear to be due to the accumulation of lipid metabolites in the membrane. Different agents, such as calcium-antagonists, beta-adrenoceptor blockers, angiotensin converting enzyme inhibitors, metabolic interventions and antioxidants, have been reported to exert beneficial effects in preventing subcellular remodeling and cardiac dysfunction in chronic diabetes. Clinical and experimental investigations have suggested that increased sympathetic activity, activated cardiac renin-angiotensin system, myocardial ischemia/functional hypoxia and elevated levels of glucose for a prolonged period, due to insulin deficiency, result in oxidative stress. It is proposed that oxidative stress associated with a deficit in the status of the antioxidant defense system may play a critical role in subcellular remodeling, calcium-handling abnormalities and subsequent diabetic cardiomyopathy.
慢性糖尿病患者的心脏功能障碍已被观察到与肌原纤维腺苷三磷酸酶活性降低以及肌浆网和肌膜钙转运过程异常有关。已有证据表明，肌球蛋白同工酶和调节蛋白表达的改变以及肌球蛋白磷酸化有助于糖尿病心脏肌原纤维重塑的发展。肌浆网和肌膜钙转运缺陷似乎是由于脂质代谢产物在膜中的积累。据报道，不同的药物，如钙拮抗剂、β肾上腺素能受体阻滞剂、血管紧张素转换酶抑制剂、代谢干预措施和抗氧化剂，在预防慢性糖尿病患者的亚细胞重塑和心脏功能障碍方面具有有益作用。临床和实验研究表明，由于胰岛素缺乏，交感神经活动增加、心脏肾素-血管紧张素系统激活、心肌缺血/功能性缺氧以及长期血糖水平升高会导致氧化应激。有人提出，与抗氧化防御系统状态不足相关的氧化应激可能在亚细胞重塑、钙处理异常及随后的糖尿病心肌病中起关键作用。
