miR-126靶向Spred-1调控血管新生治疗糖尿病性心肌病的分子机制研究

为了阐明miR-126在糖尿病性心肌病发病和干预中的作用及其分子机制，本课题首先在高糖培养的小鼠心脏微血管内皮细胞（MCMECs）中观察miR-126沉默、Spred-1沉默、miR-126并Spred-1沉默、pre-miR-126过表达、Spred-1过表达及pre-miR-126并Spred-1过表达对细胞增殖、迁移、管型形成、凋亡、氧化应激和炎症反应以及下游信号通路的影响，明确miR-126对MCMECs的作用及其分子机制。然后，在糖尿病性心肌病C57BL/6小鼠中观察糖尿病对心肌毛细血管密度及miR-126表达的影响，观察miR-126沉默、Spred-1沉默、miR-126并Spred-1沉默、pre-miR-126过表达、Spred-1过表达及pre-miR-126并Spred-1过表达对小鼠糖尿病性心肌病的作用。本课题的实施将为糖尿病性心肌病的防治提供新的靶点。

To elucidate the role and the underlying mechanisms of miR-126 in the pathogenesis and treatment of diabetic cardiomyopathy, the present study was designed to examine the effects of miR-126 knockdown, Spred-1 knockdown, knockdown of both miR-126 and Spred-1, pre-miR-126 overexpression, Spred-1 overexpression, and overexpression of both pre-miR-126 and Spred-1 on cell proliferation, migration, tube-like structure formation, apoptosis, oxidative stress, inflammatory response and downstream signaling pathways in C57BL/6 mouse cardiac microvascular endothelial cells (MCMECs), in an attempt to clarify the role of miR-126 in regulating MCMECs and its molecular mechanisms. Thereafter, streptozotocin will be intraperitoneally injected into C57BL/6 mice to produce an animal model of diabetic cardiomyopathy, which will be used to examine the effects of miR-126 silencing, Spred-1 silencing, silencing of both miR-126 and Spred-1, pre-miR-126 overexpression, Spred-1 overexpression, and overexpression of both pre-miR-126 and Spred-1 on diabetic cardiomyopathy. This project will result in a better understanding of the mechanisms underlying the pathogenesis of diabetic cardiomyopathy, which may provide novel therapeutic targets for the prevention and treatment of this disease.