长度大于200个核苷酸的长非编码RNA(lncRNA)的表达变化与神经疾病有关，但机制不清楚。心交感神经病变是糖尿病最常见的并发症之一。项目选择2型糖尿病模型大鼠颈部交感神经节（颈上和星状神经节）表达增加的lncRNA-US进行研究。项目假设高糖炎性状态下可激活颈部交感神经节神经元P2X4受体，通过P2X4-NLRP1、NLRP3炎性小体依赖的信号通路诱发IL-1β释放介导颈部交感神经节神经细胞焦亡/凋亡，引起心交感神经重构导致心功能损害。预实验提示lncRNA-US与P2X4受体存在相互作用，进一步推测lncRNA-US可能正性调控P2X4受体介导的效应，加重心交感神经损伤。实验用2型糖尿病动物模型、高糖培养细胞损伤模型，观察lncRNA-US及其shRNA对颈部交感神经节P2X4受体介导心交感功能病理变化的作用及可能机制，为糖尿病心交感神经损伤的机制及防治研究提供新的实验基础。

Changes of expression and regulating factor in long non coding RNAs (lncRNAs) (more than 200 nucleotides in length) are related with nevous diseases, but its mechanism is unknown. Diabetic cardiac sympathetic neuropathy is a very common complication. On the groundwork of previous studies, our studies select an lncRNA (preliminary name as lncRNA-US) of the upregulated expression in the cervical sympathetic ganglia (superior cervical ganglia and stellate ganglia) of type 2 diabetic rat model. Project presumes that the inflammatory state of hyperglycemia will activate the P2X4 receptor in the neurons of the cervical sympathetic ganglia, which induce that P2X4-NLRP1 or NLRP3 inflammasome signal pathway will mediate IL-1β release, and then drive pyroptosis-apoptosis in the cervical sympathetic nerves. The pyroptosis-apoptosis in the cervical sympathetic nerves results in the cardiac autonomic nerve remoding and the cardiac functional damage. Pre experiment showed that lncRNA-US interacted with the P2X4 receptor, and this project futher assumes that lncRNA-US may play a positive regulatory role in P2X4 receptor mediated-pathological changes of cardiac sympathetic damage. By application of diabetic rat model and cell model treated with high sugar, our studies will observe the effects of lncRNA-US and its shRNA on the pathological changes of cardiac dysfunction mediated by the P2X4 receptor in the cervical sympathetic ganglia and its mechanism. The research will provide new ideas to explore the pathological mechanism and the effective preventive and therapeutic measures against the occurrence of diabetic cardiac sympathetic neuropathy.