中央杏仁核lncRNA-XR_596518靶向miR-128-3p调控SIRT1参与慢性痛相关抑郁情绪的机制研究

LncRNA芯片结果显示中央杏仁核（CeA）lncRNA-XR_596518可能参与慢性痛相关抑郁情绪的调控，生物信息学及预实验提示，miR-128-3p可能是XR_596518调控痛相关抑郁情绪的关键环节，而SIRT1可能是miR-128-3p的下游靶基因。课题组前期研究证实SIRT1参与调控慢性痛相关抑郁情绪，且主要表达于CeA中GABA能神经元。因此，我们推断：CeA中XR_596518下调，导致与其靶向结合的miR-128-3p上调，进而下调SIRT1，影响GABA能神经元活化，诱发痛相关抑郁情绪。本项目拟采用SNI神经病理性疼痛大鼠、XR_596518条件性基因敲除大鼠等，应用生物信息学、分子生物学、电生理学及光遗传学等技术，阐明XR_596518通过靶向miR-128-3p调控SIRT1介导的GABA能神经元活化的分子机制，为研发防治慢性痛相关抑郁情绪的药物提供新的靶点和思路。

Microarray analysis of long non-coding RNA (lncRNA) shows that lncRNA-XR_596518 in central amygdala (CeA) may be involved in chronic pain-related depressive emotion. Bioinformatics and preliminary results suggest that miR-128-3p may be a key factor for XR_596518 to regulate chronic pain-related depressive emotion, while SIRT1 may be the target gene of miR-128-3p. Our previous study shows that SIRT1 plays an important role in the development of chronic pain-related depressive emotion, and SIRT1 mainly expresses in GABAergic neurons in CeA. Therefore, we hypothesize that the down-regulated XR_596518 expression in CeA could increase miR-128-3p expression and further decrease SIRT1 expression and influence the activation of GABAergic neurons, leading to the development of pain-related depressive emotion. Therefore, the current project is aimed to clarify the new mechanisms for XR_596518 to regulate SIRT1-mediated activation of GABAergic neurons by targeting miR-128-3p with bioinformatic, molecular biological, electrophysiological and optogenetic techniques, using spared nerve injury (SNI)-induced neuropathic pain rats and XR_596518 conditioned knockout rats. This study will provide a new potential target for the discovery of new drugs in relieving chronic pain-related depressive emotion.