基于 miR23b-NOX4调控氧化损伤研究电针治疗慢性疼痛的机理

Chronic pain is a great threat to people health.Research has proved that microRNA regulation exists in pain states .There is a close relation between chronic pain and the GABAergic neuron injure of oxidative stress regulated by miR23b-NOX4.Sciatica is the most common chronic pain,and clinic research has proven that acupuncture of“Huantiao(GB30)”、“Yanglingquan(GB34)”points is an effective treatment of sciatica. Our previous research showed the mechanism of acupuncture analgesia is relative with improving the neuron plasticity .The aim of the research is to discuss the electro-acupuncture “Huantiao”and“Yanglingquan” analgisa mechanism which is relative to anti-oxidative stree injure effect of GABAergic neurons of spinal doral horn regulated by miR23b-NOX4 . Firstly chronic constrictive injury (CCI) rat model is used to explore whether the analgesia target of elctroacupuncture is miR23b which induce oxidative injure to GABAergic neurons ,and the target of electroacupuncture analgesia is proved reversely by the model of anti-miR23b injection.The indice include pain behavior,GABAergic neurons function,oxdative stress and the expression of miR23b,NOX4. The research result would play a import role in elucidating the mechanism of electroacupuncture analgesia.

慢性疼痛严重威胁人类健康。研究表明，microRNAs参与慢性疼痛的调控，其中miR23b-NOX4调控的γ氨基丁酸（GABA）能神经元氧化应激反应与慢性疼痛关系密切。坐骨神经痛是最常见的慢性疼痛，临床研究已证明针刺“环跳”、“阳陵泉”治疗坐骨神经痛的疗效。前期工作基础表明，电针镇痛与改善神经元可塑性有关。本课题以坐骨神经痛模型为载体，以microRNA调控为切入点，研究电针镇痛的机制。研究方案首先采用坐骨神经结扎模型，研究电针“环跳”、“阳陵泉”对miR23b-NOX4调控的GABA能神经元氧化损伤的影响，其次采用反义miR23b模型对电针作用靶点进行反证。具体指标包括疼痛行为学、GABA能神经元功能、氧化损伤、miR23b和NOX4表达等。研究结果对阐明电针镇痛的机制具有重要意义。

慢性疼痛不仅给患者带来躯体和精神上的痛苦，同时加重家庭和社会的经济负担。研究表明，microRNAs参与慢性疼痛的调控，其中miR23b-NOX4调控的γ氨基丁酸（GABA）能神经元氧化应激反应与慢性疼痛关系密切。坐骨神经痛是最常见的慢性疼痛，临床研究已证明针刺“环跳”、“阳陵泉”治疗坐骨神经痛的疗效。本课题以坐骨神经痛模型为载体，以microRNA调控为切入点，研究电针镇痛的机制。研究结果显示：1.电针“GB30”-“GB34”及miR23b可以改善CCI动物的痛敏状态，电针镇痛效果优于注射miR23b组。2.电针“GB30”-“GB34”及miR23b可以上调疼痛引起的GABA（A）、（B）受体、GAD67mRNA的表达下降及血清GABA含量下降；上调疼痛引起的大鼠脊髓背角GABA、GABAB、GAD67阳性表达下降, 从而调整两种疼痛模型大鼠脊髓背角GABA能神经元功能。3本实验中两种疼痛模型都引起miR23b表达下降，其调控靶点NOX4表达增高，导致GABA能神经元受到氧化损伤而功能受损。电针“GB30”-“GB34”及注射miR23b可以调整两种疼痛模型大鼠脊髓背角GABA能神经元功能，有抗氧化损伤作用，可以调整疼痛引起的miR23及NOX4的改变。4.血清代谢组学结果显示，电针通过调控亚麻脂酸、不饱和脂肪酸、嘧啶、牛磺酸和亚牛磺酸、维生素B6等物质代谢，起到止痛的作用。.因此：电针“GB30”-“GB34”通过调控miR23b- NOX4抑制GABA能神经元氧化损伤，达到镇痛的作用。