运动及复杂环境抑制细菌脂多糖诱导的中脑黑质多巴胺能神经元损伤

Exercise and complex environment inhibiting lipopolysaccharide-induced dopaminergic neuron damage in substantia nigra

目的探讨运动和复杂环境对细菌脂多糖(LPS)诱导的中脑黑质多巴胺能神经元死亡的影响。方法将C57BL/6小鼠分为对照组、LPS组、LPS+游泳组和LPS+复杂环境组,每组各7只。LPS组小鼠通过脑立体定位注射建立帕金森病炎症模型,置于鼠笼中生活2周。LPS+游泳组小鼠模型制作后每日强迫进行游泳运动15 min,运动2周。LPS+复杂环境组小鼠模型制作后置于复杂环境生活2周。对照组小鼠不做处理。模型制作14 d后,对各组小鼠进行足迹、旷场和滚轴等行为学实验,检测小鼠的自主运动能力、运动平衡能力和抑郁水平;免疫组织化学染色和Western blotting检测中脑黑质中酪氨酸羟化酶(TH)的表达;Western blotting检测中脑黑质中脑源性神经生长因子(BDNF)、Caspase-3、白细胞介素(IL)-1β、IL-6和肿瘤坏死因子α(TNF-α)的表达;RT-PCR检测中脑黑质中IL-1β、IL-6和TNF-α转录水平。结果与对照组相比,LPS组、LPS+游泳组、LPS+复杂环境组小鼠的运动能力和平衡能力均有所下降,抑郁水平有所上升(P<0.001),TH阳性神经元存活数量和BDNF蛋白量均显著减少(P<0.001),Caspase-3及IL-1β、IL-6和TNF-α含量均显著增高(P<0.001)。与LPS组相比,LPS+游泳组和LPS+复杂环境组小鼠的运动能力和平衡能力均有所恢复,抑郁水平显著下降(P<0.01),TH阳性神经元存活数量及BDNF含量均显著增多(P<0.01),Caspase-3及IL-1β、IL-6和TNF-α均显著减少(P<0.01),且LPS+复杂环境组现象更为显著。结论运动和复杂环境能抑制LPS诱导的小鼠中枢神经系统炎症,从而减轻对中脑黑质神经元的损伤,且LPS+复杂环境组的抑制效果更为显著。

Objective To investigate the effects of exercise and complex environment on lipopolysaccharide(LPS)-induced dopaminergic neuron death in the substantia nigra of midbrain.Methods C57BL/6 mice were divided into control group,LPS group,LPS+swimming group and LPS+complex environment group,with 7 mice in each group.The mice in the LPS group were injected with LPS into the brain to establish an inflammatory model of Parkinson’s disease and lived in cages for 2 weeks.Mice in LPS+swimming group were forced to swim for 15 minutes every day for 2 weeks after modeling.The mice in the LPS+complex environment group were placed in a complex environment for 2 weeks after modeling.The control group mice were not treated.After 14 days of modeling,behavioral experiments such as footprint,open field and rotating rod were performed on each group of mice to detect the autonomous exercise ability,exercise balance ability and depression level of mice.The expressions of tyrosine hydroxylase(TH)in substantia nigra was detected by immunohistochemical staining and Western blotting.The expressions of brain-derived neurotrophic factor(BDNF),Caspase-3,interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the substantia nigra of the midbrain were detected by Western blotting.The transcription levels of IL-1β,IL-6 and TNF-αin substantia nigra were detected by RT-PCR.Results Compared with the control group,the exercise ability and balance ability of mice in LPS group,LPS+swimming group and LPS+complex environment group decreased,the depression level increased(P<0.001),the number of TH positive neurons and BDNF protein decreased significantly(P<0.001),and the contents of Caspase-3,IL-1β,IL-6 and TNF-αincreased significantly(P<0.001).Compared with the LPS group,the exercise ability and balance ability of the mice in the LPS+swimming group and the LPS+complex environment group were restored,the depression level decreased significantly(P<0.01),the survival number of TH positive neurons and the content of BDNF increased significantly(P<0.01),Caspase-3,IL-1β,IL-6 and TNF-αreduced significantly(P<0.01),and the phenomenon in the LPS+complex environment group was more significant.Conclusion Exercise and complex environment can inhibit LPS-induced central nervous system inflammation in mice,thereby reducing damage to midbrain substantia nigra neurons,and the inhibitory effect of LPS+complex environment group is more significant.