Tate Mitchel, Deo Minh, Cao Anh H, Hood Sally G, Huynh Karina, Kiriazis Helen, Du Xiao-Jun, Julius Tracey L, Figtree Gemma A, Dusting Gregory J, Kaye David M, Ritchie Rebecca H
1 Heart Failure Pharmacology Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, Australia.
2 Centre for Inflammatory Diseases, Monash University and Monash Medical Centre, Clayton, VIC, Australia.
Diab Vasc Dis Res. 2017 Sep;14(5):423-433. doi: 10.1177/1479164117710390. Epub 2017 May 31.
Diabetic cardiomyopathy is a major contributor to the increasing burden of heart failure globally. Effective therapies remain elusive, in part due to the incomplete understanding of the mechanisms underlying diabetes-induced myocardial injury. The objective of this study was to assess the direct impact of insulin replacement on left ventricle structure and function in a rat model of diabetes. Male Sprague-Dawley rats were administered streptozotocin (55 mg/kg i.v.) or citrate vehicle and were followed for 8 weeks. A subset of diabetic rats were allocated to insulin replacement (6 IU/day insulin s.c.) for the final 4 weeks of the 8-week time period. Diabetes induced the characteristic systemic complications of diabetes (hyperglycaemia, polyuria, kidney hypertrophy) and was accompanied by marked left ventricle remodelling (cardiomyocyte hypertrophy, left ventricle collagen content) and diastolic dysfunction (transmitral E/A, left ventricle-dP/dt). Importantly, these systemic and cardiac impairments were ameliorated markedly following insulin replacement, and moreover, markers of the diabetic cardiomyopathy phenotype were significantly correlated with the extent of hyperglycaemia. In summary, these data suggest that poor glucose control directly contributes towards the underlying features of experimental diabetic cardiomyopathy, at least in the early stages, and that adequate replacement ameliorates this.
糖尿病性心肌病是全球心力衰竭负担不断增加的主要原因。有效的治疗方法仍然难以捉摸，部分原因是对糖尿病诱导心肌损伤的潜在机制了解不全面。本研究的目的是评估胰岛素替代对糖尿病大鼠模型左心室结构和功能的直接影响。给雄性斯普拉格-道利大鼠静脉注射链脲佐菌素（55mg/kg）或柠檬酸盐载体，并持续观察8周。在8周时间段的最后4周，将一部分糖尿病大鼠分配到胰岛素替代组（皮下注射胰岛素6IU/天）。糖尿病诱发了糖尿病的典型全身并发症（高血糖、多尿、肾脏肥大），并伴有明显的左心室重塑（心肌细胞肥大、左心室胶原含量）和舒张功能障碍（二尖瓣E/A、左心室-dP/dt）。重要的是，胰岛素替代后这些全身和心脏损伤得到显著改善，此外，糖尿病性心肌病表型的标志物与高血糖程度显著相关。总之，这些数据表明，至少在早期阶段，血糖控制不佳直接导致实验性糖尿病性心肌病的潜在特征，而适当的替代治疗可改善这一情况。
