Gas6通过Tyro3受体促进糖尿病大鼠施万细胞形成髓鞘的机制研究

糖尿病周围神经病变(DPN)是糖尿病常见的并发症之一，施万细胞形成髓鞘减少与DPN的发生发展有密切关系。在预实验中，本课题组发现外源性生长停滞特异性蛋白6(Gas6)通过与Tyro3受体结合，对高糖培养的施万细胞髓鞘零蛋白(MPZ)、髓鞘碱性蛋白(MBP)下调具有改善作用。结合文献，我们提出如下假说“Gas6与Tyro3受体结合后，依赖于Tyro3/Fyn/Akt/Oct6&Krox20通路引起施万细胞MPZ、MBP表达增加。Gas6通过以上通路改善DPN大鼠坐骨神经脱髓鞘病变。Gas6、Tyro3表达水平与DPN症状相关。改变Gas6、Tyro3表达水平影响MPZ、MBP的表达。”本项目拟采用施万细胞及DRG神经元共培养，DPN大鼠为研究对象，应用细胞转染、免疫荧光、透射电镜、电生理检测、行为学等方法，探讨Gas6/Tyro3在DPN进程中的作用及相关分子机制，为DPN的治疗寻找靶点。

Diabetic peripheral neuropathy (DPN) is one of the common complications of diabetes. The decrease of myelin formation in schwann cells is closely related to the occurrence and development of DPN. In pre-experiments, we found that exogenous growth arrest-specific 6(Gas6) can improve the down-regulation of myelin zero protein (MPZ) and myelin basic protein (MBP) of schwann cells cultured in high glucose by binding to Tyro3 receptor. Combined with references, we hypothesized that“Gas6 could bind to the Tyro3 receptor, and increase the expression of MPZ and MBP in schwann cells through the Tyro3/Fyn/Akt/Oct6&Krox20 pathway. Gas6 could improve the demyelination of sciatic nerve in DPN rats through the above pathway. The expression of Gas6 and Tyro3 could be correlated with DPN symptoms.The expression of MPZ and MBP could be affected by the changes of Gas6 and Tyro3.”Through cocultivation of schwann cells and DRG neurons, DPN rats as research object, integrated application of cell transfection, immunofluorescence, transmission electron microscopy, electrophysiological detection, and behavioral experiment, we will further study the role of Gas6 / Tyro3 in the process of DPN and relevant molecular mechanisms, and look for new targets for the treatment of DPN.