芦丁钠在慢性疼痛抑郁共病中的预防和治疗作用研究

Preventive and the rapeutic effect of sodium rutin(NaR)for comorbid depressive symptoms in chronic pain

目的评价芦丁钠(NaR)对选择性神经损伤(SNI)模型诱导的慢性疼痛抑郁共病的作用及细胞机制。方法通过SNI手术构建C57BL/6J小鼠慢性疼痛抑郁共病模型,将小鼠分为SNI模型组和SNI模型给予NaR(SNI+NaR)组,假手术(Sham)组作为对照组。通过Von Frey纤维丝检测小鼠机械痛(PWT),悬尾测试(TST)和强迫游泳测试(FST)评价小鼠的抑郁样行为。采用免疫荧光染色检测内侧前额叶皮质小胶质细胞数量。结果与Sham组相比,SNI组小鼠术后50%PWT显著降低(P<0.001);术后28 d小鼠FST和TST不动时间显著增加(P<0.001),表现出抑郁样行为;SNI术后45 d,SNI组小鼠内侧前额叶皮质小胶质细胞数量增多(P<0.05)。与SNI模型组相比,术后立即给予NaR小鼠,给药3 d后50%PWT值显著增大(P<0.01),连续给药28 d后小鼠TST和FST不动时间显著减少(P<0.05)。术后28 d抑郁样行为出现后给予NaR小鼠,给药1周后FST不动时间显著减少(P<0.001),给药2周后TST不动时间显著减少(P<0.001),给药2周后内侧前额叶皮质小胶质细胞数量显著减少(P<0.05)。结论NaR在SNI模型诱导的慢性疼痛抑郁共病小鼠中具有镇痛和抗抑郁作用,逆转小胶质细胞的增殖可能是其产生抗抑郁作用的机制之一。

Objective To explore the effect of sodium rutin(NaR)on comorbid depressive symptoms(CDS)in chronic pain induced by selected neurological injury(SNI).Methods A model of comorbid depressive symptoms in chronic pain was established using C57BL/6J mice by SNI.The modeled mice were divided into two groups:a SNI model group and a SNI+NaR group.Those undergoing sham operation were defined as control group.Then,their mechanical pain was assessed by Von Frey fibers.Depression-like behaviors were evaluated by the forced swimming test(FST)and the tail suspension test(TST).The number of microglia in the medial prefrontal cortex was detected by immunofluorescence.Results Compared with the Sham group,the SNI group showed significantly reduced threshold of foot contraction(P<0.001),remarkably extended immobility time of the FST and TST 28 days after surgery(P<0.001),with depression-like behaviors;and an increased number of IBA1+microglia in mPFC of mice(P<0.05).Compared with the SNI group,the SNI+NaR group,which was given NaR immediately after surgery,showed significant increases of the 50%paw withdrawal threshold(PWT)(P<0.01)and increases in the immobility time of FST and TST when continuous treatment for 28 days(P<0.05).The mice,which shown depression-like behaviors,were administered NaR 28 days after surgery,while the immobility time of FST was significantly reduced after 1 week NaR administration(P<0.001),and TST immobility time was significantly reduced after 2 weeks of NaR administration(P<0.001).The number of microglia in the medial prefrontal cortex two weeks after treatment significantly decreased(P<0.05).Conclusions Under the condition of SNI model,NaR relieves the chronic pain and improves behaviors of depression.NaR reversed the increase of microglia number in the mPFC,which may be one of the mechanisms of its antidepressant effect.