Neuregulin-1/ErbB信号传导系统在缺血性心脏病心肌血管重构中的作用及机制

项目名称： Neuregulin-1/ErbB信号传导系统在缺血性心脏病心肌血管重构中的作用及机制

项目编号： No.81460063

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 桂春

作者单位： 广西医科大学

项目金额： 47万元

中文摘要： 促进心肌血管形成和重构对于缺血性心脏病具有重要意义。Neuregulin-1(NRG1)/ErbB信号传导在心脏中起着非常广泛的作用，但该信号传导在心脏血管形成和重构方面的作用无研究报道。我们前期研究显示，给予NRG1治疗可显著提高糖尿病心肌VEGF的表达，增加Flk受体和eNOS的磷酸化。我们研究还显示冠状动脉平滑肌细胞和心脏微血管内皮细胞能表达ErbB2、ErbB3和ErbB4受体。这些都提示NRG1/ErbB信号传导在心肌血管重构中起着一定的作用。所以本研究将建立心肌慢性缺血和急性梗死模型，运用NRG1基因敲除小鼠、NRG1基因转染和siRNA技术，及 PET、同位素标记微球、细胞培养、免疫组化和Western blot等方法，检测在心肌慢性缺血和急性梗死中，NRG1/ErbB信号传导对心肌血管形成和重构的作用，并探讨其分子机制，为探索新的预防和治疗方法奠定基础。

中文关键词： 缺血性心脏病；血管重构；血管生成；Neuregulin-1；ErbB受体

英文摘要： Promote myocardial vascular formation and remodeling is of great significance for ischemic heart disease. Neuregulin-1(NRG1)/ErbB signaling plays the widely roles in the heart, but little studies have reported the effects of this signal transduction on vascular formation and remodeling in the heart. Our previous studies have shown that the expression of VEGF and the phosphorylation of Flk receptor and eNOS were increased in myocardial tissue of diabetic rats with NRG1 treatment. Our previous studies have also shown that ErbB2, ErbB3 and ErbB4 receptors were expressed in coronary artery smooth muscle cells and cardiac microvascular endothelial cells. All of these indicate that NRG1/ErbB signaling system may play some roles in myocardial vascular remodeling. So by establishing the chronic myocardial ischemia and acute myocardial infarction model, using NRG1 gene knockout mice, NRG1 gene transfection and siRNA technology, and PET, stable isotope labeling microspheres, cell culture, immunohistochemistry and Western blot methods, this study will detect the effects of NRG1/ErbB signaling on vascular formation and remodeling in myocardium of chronic ischemia and acute infarction, and explore its molecular mechanisms, so as to lay a good foundation for exploring new methods of prevention and treatment.

英文关键词： Ischemic heart disease;Vascular remodeling;angiogenesis;Neuregulin-1;ErbB receptors