乳酸对慢性神经病理性痛小鼠认知功能的影响

Effect of lactic acid on cognitive function in mice with chronic neuropathic pain

目的探索乳酸对慢性神经病理性痛小鼠认知功能的影响。方法选择C57BL/6J雄性小鼠36只,8~10周龄,体重25~30 g。采用坐骨神经损伤(SNI)制备慢性神经病理性痛模型。将小鼠随机分为三组:假手术组(Sham组)、坐骨神经损伤组(SNI组)和坐骨神经损伤+乳酸处理组(SNIL组),每组12只。Sham组仅暴露神经,不进行结扎处理。SNI组和SNIL组制备慢性神经病理性痛模型。乳酸通过生理盐水稀释至终浓度100 mg/ml。SNIL组于手术当天至术后第20天每天腹腔注射乳酸0.25 ml。Sham组和SNI组在相同时点给予等体积生理盐水。于手术当天和术后第21天测量MWT,于术后第20天采用旷场实验测量运动距离,采用新物体识别实验计算新物体探索时间百分比。于术后第21天采用Y迷宫实验计算轮替率。术后第22天处死小鼠,采用Western blot法检测脑源性神经营养因子(BDNF)、早期生长反应因子-1(Egr-1)和细胞骨架活性调节蛋白(Arc)的相对含量。结果与Sham组比较,SNI组和SNIL组术后第21天MWT明显降低,SNI组新物体探索时间百分比明显降低,轮替率、海马组织BDNF、Egr-1、Arc相对含量明显降低(P<0.05)。与SNI组比较,SNIL组新物体探索时间明显延长,轮替率、海马组织BDNF、Egr-1、Arc相对含量明显升高(P<0.05)。结论乳酸可以通过增加慢性神经病理性痛小鼠海马突触可塑性相关蛋白的表达,减轻认知功能损伤。

Objective To explore the effect of lactic acid on cognitive function in mice with chronic neuropathic pain.Methods Chronic neuropathic pain model was established by sciatic nerve injury(SNI).Thirty-six male C57BL/6J mice,aged 8 to 10 weeks,weight 25 to 30 g,were randomly divided into three groups(n=12):group Sham,group SNI and SNI+lactic acid treatment group(group SNIL).In group Sham,only the nerves were exposed and no ligation was performed.Chronic neuropathic pain model was prepared in group SNI and group SNIL.Lactic acid was diluted with normal saline to a final concentration of 100 mg/ml.In group SNIL,lactate 0.25 ml was intraperitoneally injected daily from the day of surgery to the 20th day after surgery.Group Sham and group SNI were given equal volume normal saline at the same time.The MWT was measured on the day of surgery and the 21st day after surgery.On the 20th day after surgery,the moving distance was measured by open field experiment,and the percentage of new object exploration time was calculated by new object recognition experiment.The alternation rate was calculated by Y maze test on the 21st day after surgery.The mice were sacrificed on the 22nd day and the relative protein contents of brain-derived neurotrophic factor(BDNF),early growth response factor-1(Egr-1)and activity regulated cytoskeleton(Arc)were detected by Western blot.Results Compared with group Sham,MWT in groups SNI and SNIL decreased significantly on day 21 after operation,and in group SNI,the discovery time of new objects was significantly shortened,and the alternation rate,the relatively contents of BDNF,Egr-1 and Arc protein in hippocampus were significantly decreased(P<0.05).Compared with group SNI,the discovery time of new objects in group SNIL was significantly extended,and the alternation rate,the contents of BDNF,Egr-1 and Arc protein in hippocampus were significantly increased(P<0.05).Conclusion Lactic acid can reduce cognitive impairment of mice with chronic neuropathic pain by increasing the expression of synaptic plasticity related proteins in hippocampus.