心肌冲动传播在 Zucker 糖尿病肥胖（ZDF）大鼠的右心室组织中受损。
Myocardial impulse propagation is impaired in right ventricular tissue of Zucker diabetic fatty (ZDF) rats.
机构信息
The Danish National Research Foundation Centre for Cardiac Arrhythmia and Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen DK-2200, Denmark.
出版信息
Cardiovasc Diabetol. 2013 Jan 17;12:19. doi: 10.1186/1475-2840-12-19.
BACKGROUND
Diabetes increases the risk of cardiovascular complications including arrhythmias, but the underlying mechanisms remain to be established. Decreased conduction velocity (CV), which is an independent risk factor for re-entry arrhythmias, is present in models with streptozotocin (STZ) induced type 1 diabetes. Whether CV is also disturbed in models of type 2 diabetes is currently unknown.
METHODS
We used Zucker Diabetic Fatty (ZDF) rats, as a model of type 2 diabetes, and their lean controls Zucker Diabetic Lean (ZDL) rats to investigate CV and its response to the anti-arrhythmic peptide analogue AAP10. Gap junction remodeling was examined by immunofluorescence and western blotting. Cardiac histomorphometry was examined by Masson`s Trichrome staining and intracellular lipid accumulation was analyzed by Bodipy staining.
RESULTS
CV was significantly slower in ZDF rats (56±1.9 cm/s) compared to non-diabetic controls (ZDL, 66±1.6 cm/s), but AAP10 did not affect CV in either group. The total amount of Connexin43 (C×43) was identical between ZDF and ZDL rats, but the amount of lateralized C×43 was significantly increased in ZDF rats (42±12 %) compared to ZDL rats (30±8%), p<0.04. Judged by electrophoretic mobility, C×43 phosphorylation was unchanged between ZDF and ZDL rats. Also, no differences in cardiomyocyte size or histomorphometry including fibrosis were observed between groups, but the volume of intracellular lipid droplets was 4.2 times higher in ZDF compared to ZDL rats (p<0.01).
CONCLUSION
CV is reduced in type 2 diabetic ZDF rats. The CV disturbance may be partly explained by increased lateralization of C×43, but other factors are likely also involved. Our data indicates that lipotoxicity potentially may play a role in development of conduction disturbances and arrhythmias in type 2 diabetes.
背景
糖尿病增加了心血管并发症的风险，包括心律失常，但潜在的机制仍有待确定。链脲佐菌素（STZ）诱导的 1 型糖尿病模型中存在传导速度（CV）降低，这是折返性心律失常的独立危险因素。2 型糖尿病模型中 CV 是否也受到干扰目前尚不清楚。
方法
我们使用 Zucker 糖尿病肥胖（ZDF）大鼠作为 2 型糖尿病模型及其 lean 对照 Zucker 糖尿病瘦（ZDL）大鼠，研究 CV 及其对抗心律失常肽类似物 AAP10 的反应。通过免疫荧光和 Western blot 检测缝隙连接重塑。通过 Masson's Trichrome 染色检查心脏组织形态计量学，通过 Bodipy 染色分析细胞内脂质积累。
结果
ZDF 大鼠的 CV 明显较慢（56±1.9 cm/s），而非糖尿病对照组 ZDL 大鼠的 CV 为 66±1.6 cm/s，但 AAP10 对两组大鼠的 CV 均无影响。ZDF 大鼠和 ZDL 大鼠的 Connexin43（C×43）总量相同，但 ZDF 大鼠的侧向 C×43 明显增多（42±12%），而 ZDL 大鼠的侧向 C×43 明显增多（30±8%），p<0.04。通过电泳迁移率判断，ZDF 大鼠和 ZDL 大鼠的 C×43 磷酸化无差异。此外，两组间的心肌细胞大小或组织形态学（包括纤维化）无差异，但 ZDF 大鼠的细胞内脂质滴体积比 ZDL 大鼠高 4.2 倍（p<0.01）。
结论
2 型糖尿病 ZDF 大鼠的 CV 降低。CV 紊乱部分可能是由于 C×43 的侧向化增加所致，但也可能涉及其他因素。我们的数据表明，脂毒性可能在 2 型糖尿病的传导障碍和心律失常的发展中发挥作用。
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