长非编码RNA-UG在背根神经节嘌呤2Y14受体介导糖尿病神经病理痛的作用及机制研究

Changes of expression and regulating factor in long noncoding RNAs (lncRNAs) (more than 200 nucleotides in length) are related with diseases, but its mechanism is unknown. Diabetic neuropathic pain (DNP) is a very common complication, which causes considerable suffering and is difficult to treat. Our previous studies showed that lncRNAs (>200 nt) in rat dorsal root ganglia (DRG) have been identified by transcriptome database verification and sequence predication screening of SOLiD highthroughput. According to preliminary experiments, we select an lncRNA (preliminary name as lnc-UG) of the upregulated expression in DRG of type 2 diabetic rat model. Preliminary experiment showed the P2Y14 expression was significantly higher in the DNP group than in the control group. Interestingly, pain sensitivity in rat model treated with short hairpin RNA (shRNA) against lnc-UG was significantly decreased. Consistent with reducing pain behaviors, P2Y14 expression in DRG in rat model was significantly reduced in response to the treatment using a shRNA against lnc-UG. Preliminary experiments suggest that lnc-UG may positively regulate the expression of P2Y14 receptor. This project will further explore the mechanisms underlying the beneficial effect of lnc-UG shRNA and the application of nano materials for drug / gene collaborative targeting drug delivery system on the DNP mediated by P2Y14 receptor in rats. The research will provide new ideas to explore the mechanism and effective therapeutic targets for the occurrence of DNP.

长度大于200个核苷酸的长非编码RNA(lncRNA)的表达变化与疾病有关，但机制不清楚。糖尿病神经病理痛(DNP)是最常见并难治并发症。前期用SOLiD高通量大鼠转录组数据库验证和序列预测筛选出背根神经节(DRG)中大于200nt的lncRNAs。项目选择2型糖尿病模型大鼠DRG表达增加的lnc-UG进行研究。DNP大鼠DRG中P2Y14受体表达增高。Lnc-UG短发夹RNA(shRNA)处理后，模型大鼠DRG中P2Y14受体表达下调，缓解糖尿病模型大鼠痛敏。预实验显示lnc-UG可正性调控P2Y14受体的表达。本项目观察lnc-UGshRNA、及天然药物单体/lnc-UGshRNA整合的纳米材料性协同靶向给药对DRG中P2Y14受体介导DNP的作用及可能机制，从而为DNP发生机制及有效防治靶点探究提供新思路。

大鼠背根神经节和脊髓P2Y14受体参与糖尿病神经病理痛过程，P2Y14 shRNA可缓解2型糖尿病大鼠神经病理痛；LncRNA-UC.25+ shRNA可以缓解P2Y14受体介导的糖尿病神经病理痛；LncRNA-UC.25+可能通过直接或间接调控DRG卫星胶质细胞和脊髓小胶质细胞中的P2Y14受体从而介导DNP；LncRNA-UC.25+可能通过转录因子STAT1调控P2Y14受体而缓解DNP。