糖尿病脑病是糖尿病严重的慢性并发症，以认知功能障碍为特征，其病变机制未明，研究发现高血糖损害海马神经元Ca2+稳态导致神经退行性病变，N-甲基-D-天门冬氨酸（NMDA）受体参与该病理过程，而肌球蛋白轻链激酶（MLCK）是钙信号通路的关键分子之一，课题组前期发现MLCK在糖尿病脑病大鼠脑组织海马神经元表达增高，提示其可能参与了糖尿病脑病的发生发展。本课题拟以MLCK的编码基因mylk1为靶点，对糖尿病BB Wistar大鼠和Wistar大鼠海马神经元细胞进行研究，分析敲除mylk1基因、mylk1过表达和RNAi后对神经元细胞骨架、Ca2+-CaM-CaMKⅡ以及NMDA受体的影响，从整体、细胞水平和分子水平揭示MLCK在糖尿病脑病发生发展中的作用。该项目将有助于加深MLCK在糖尿病脑病发病机制中的认识，也为糖尿病脑病的诊断和治疗提供新的靶标。

Diabetic encephalopathy characterized by cognitive dysfunctionis is a serious chronic complication of diabetes. And its pathogenesis is unclear . Previous studies reveal that high blood glucose may cause neurodegeneration by disturbing the homeostasis of Ca2+ and NMDA (N-methyl-D-aspartate ) receptor has been found to be involved in the process. Our previous study found that MLCK (myosin light streptokinase), one of the key molecules of calcium signaling pathway, showed increased expression in hippocampal neurons of diabetic encephalopathy rats, which reveal that it may play an important role in the development and progress of diabetic encephalopathy. Here our study is designed to explore its molecular mechanism involved the diabetic encephalopathy. We will obeserve the changes of rats with diabetic encephalopathy and cultured hippocampal neurons at the conditions of overexpression , reduced expression and non-expression of MLCK by the technologies of knockout, RNAi and cell transfection. Our study will uncover the mechnism of MLCK involved the development and progress of diabetic encephalopathy .