NADPH氧化酶介导的小胶质细胞活化在神经病理性疼痛和抑郁共病中的作用

发布时间：2019-05-16 17:52

【摘要】：目的观察神经病理性疼痛和抑郁共病中磷酸酰胺腺嘌呤二核苷酸(NADPH)氧化酶及小胶质细胞的变化,并探讨其相关机制。方法采用保留性坐骨神经损伤模型(SNI模型)。健康成年雄性SD大鼠44只,随机分为四组:假手术+溶剂组(SV组)、假手术+夹竹桃麻素(APO)组(SA组)、SNI+溶剂组(SNV组)、SNI+APO组(SNA组),每组11只。SA组和SNA组术前24h及术前1h腹腔注射APO 15mg/kg,以后每天注射1次直至SNI术后14d;其余两组在相同时点注射等容量溶剂。术前1d和术后7、14d进行机械缩足反射阈值(MWT)测试,术后14d进行旷场实验、强迫游泳实验和糖水偏好实验等行为学测试。行为学后2h取大鼠前额叶皮层组织,采用Western blot法检测gp91~(phox)的含量,免疫荧光共标法检测Iba1和gp91~(phox)的表达量。结果与SV、SA、SNA组比较,SNV组MWT明显降低,强迫游泳不动时间明显延长,糖水消耗比例明显减少,gp91~(phox)含量明显增多(P0.05)。与SV、SA、SNA组比较,SNV组Iba1和gp91~(~(phox))表达量增多。旷场实验中,四组探索总路程差异无统计学意义;糖水偏好实验中,四组总液体消耗量差异无统计学意义。结论神经病理性疼痛可导致抑郁样行为,并引起前额叶皮层的NADPH氧化酶活化;NADPH氧化酶抑制剂APO可减轻疼痛和抑郁样行为,其机制可能与抑制小胶质细胞活化有关。
[Abstract]:Objective to observe the changes of (NADPH) oxidase and microglia in patients with neuropathic pain and depression, and to explore its related mechanism. Methods the reserved nerve injury model (SNI model) was used. Forty-four healthy adult male SD rats were randomly divided into four groups: pseudo-surgical solvent group (SV group), pseudo-operated mandarin (APO) group (SA group), SNI solvent group (SNV group), SNI APO group), SNA group). There were 11 rats in each group. APO 15 mg 路kg ~ (- 1) was injected intraperitoneally 24 hours before operation and 1 hour before operation in SA group and SNA group, and then once a day until 14 days after SNI. The other two groups were injected with the same volume solvent at the same time. The mechanical foot reflex threshold was measured by (MWT) on the 1st day before operation and 7 and 14 days after operation, and the behavior tests such as open field test, forced swimming test and sugar-water preference test were carried out on the 14th day after operation. The prefrontalis cortex of rats was taken 2 hours after behavior. the content of gp91~ (phox) was detected by Western blot method, and the expression of Iba1 and gp91~ (phox) was detected by immunofluorescence co-standard method. Results compared with SV,SA,SNA group, MWT in SNV group was significantly decreased, forced swimming immobility time was significantly prolonged, sugar and water consumption ratio was significantly decreased, and gp91~ (phox) content was significantly increased in SNV group (P 0.05). Compared with SV,SA,SNA group, the expression of Iba1 and gp91~ (phox) in SNV group was increased. In the open field experiment, there was no significant difference in the total distance between the four groups, but there was no significant difference in the total liquid consumption among the four groups in the sugar-water preference experiment. Conclusion Neuropathic pain can lead to depression-like behavior and NADPH oxidase activation in prefrontal cortex, and NADPH oxidase inhibitor APO can relieve pain and depression-like behavior, which may be related to the inhibition of microglia activation.
【作者单位】：徐州医科大学江苏省麻醉学重点实验室;南京大学医学院临床学院南京军区南京总医院麻醉科;中国人民解放军第101医院麻醉疼痛科;
【基金】：国家自然科学基金(81503053,81571083)
【分类号】：R741;R749.4

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