Department of Cardiology, the First Affiliated Hospital, Guangxi Medical University, Nanning Guangxi, People's Republic of China.
Cardiovasc Pathol. 2012 Sep-Oct;21(5):414-20. doi: 10.1016/j.carpath.2011.12.006. Epub 2012 Jan 28.
Diabetic cardiomyopathy (DCP) is one of the leading causes of increased morbidity and mortality in the diabetic population. The neuregulin-1(NRG1)/ErbB signal system plays a critical role in maintenance of adult heart function. But little is known about the changes of NRG1/ErbB signal system in DCP. The aim of this study was to investigate the changes of the NRG1/ErbB signal system in DCP.
A rat model of DCP was established using a single intraperitoneal injection of streptozotocin (STZ). Cardiac function was assessed using echocardiography. The left ventricle fibrosis was evaluated using Masson's trichrome staining. The mRNA expression profiles of ErbB2 and ErbB4 receptors were evaluated using real-time polymerase chain reaction. The protein expression of NRG1 and the phosphorylation of ErbB2 and ErbB4 receptors were assessed using Western blot analysis.
The results showed dramatic left ventricle fibrosis and impaired left ventricle systolic function at 12 weeks after STZ-induced diabetes. This study also showed that ErbB2 and ErbB4 mRNA expression and NRG1 protein expression in the left ventricular myocardium were significantly decreased. In addition, we observed decreased phosphorylation of the ErbB2 and ErbB4 receptors at 12 weeks after the induction of diabetes.
These findings suggest that NRG1/ErbB signaling is impaired in DCP, which may play some roles in the pathogenesis of DCP.
糖尿病心肌病(DCP)是糖尿病患者发病率和死亡率增加的主要原因之一。神经调节蛋白 1(NRG1)/表皮生长因子受体(ErbB)信号系统在维持成人心脏功能方面起着关键作用。但是,关于 DCP 中 NRG1/ErbB 信号系统的变化知之甚少。本研究旨在探讨 DCP 中 NRG1/ErbB 信号系统的变化。
通过单次腹腔注射链脲佐菌素(STZ)建立 DCP 大鼠模型。使用超声心动图评估心功能。使用 Masson 三色染色评估左心室纤维化。使用实时聚合酶链反应评估 ErbB2 和 ErbB4 受体的 mRNA 表达谱。使用 Western blot 分析评估 NRG1 蛋白表达和 ErbB2 和 ErbB4 受体的磷酸化。
结果表明,STZ 诱导糖尿病 12 周后,左心室纤维化和左心室收缩功能明显受损。本研究还表明,左心室心肌中 ErbB2 和 ErbB4 mRNA 表达和 NRG1 蛋白表达显著降低。此外,我们观察到糖尿病诱导 12 周后 ErbB2 和 ErbB4 受体的磷酸化减少。
这些发现表明,NRG1/ErbB 信号在 DCP 中受损,这可能在 DCP 的发病机制中起一定作用。