硫辛酸调控沉默信息调节因子1/P53通路对帕金森病动物模型的神经保护作用  

Neuroprotective effect of lipoic acid on SIRT1/P53 pathway in animal models of Parkinson's disease

作　　者：朱艳霞[1] 甄宁[1] 吕冬芳[1] 刘久志 王雪笠[1] Zhu Yanxia;Zhen Ning;Lv Dongfang;Liu Jiuzhi;Wang Xueli(Department of Neurology,Bethune International Peace Hospital/the of 980 Hospital of Joint Logistics Support Force,Shijiazhuang,Hebei 050000,China)

机构地区：[1]联勤保障部队980医院、白求恩国际和平医院神经内科,河北石家庄050000

出　　处：《中国微侵袭神经外科杂志》2023年第12期174-178,共5页Chinese Journal of Minimally Invasive Neurosurgery

摘　　要：目的研究硫辛酸调控沉默信息调节因子1(silent information regulator 1,SIRT1)/P53通路对帕金森病(Parkinson's disease,PD)动物模型的神经保护作用。方法45只雄性C517BL/6J小鼠随机分成3组:对照组、模型组、硫辛酸组。模型组、硫辛酸组均采用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导建立PD小鼠模型,其中硫辛酸组给予腹腔注射硫辛酸,模型组、对照组腹腔注射等体积生理盐水。电镜下观察3组小鼠中脑神经细胞超微结构,通过悬绳实验、旷场实验、转棒实验评估硫辛酸对PD小鼠运动缺陷的影响,评估小鼠纹状体多巴胺能神经元凋亡情况以及多巴胺(dopamine,DA)、3,4-二羟基苯乙酸(3,4-dihydroxyphenylacetic acid,DOPAC)表达水平,Western blotting法检测SIRT1/P53通路相关蛋白表达情况。结果3组小鼠总移动距离、平均运动速度、悬线实验评分、下落潜伏期差异有统计学意义(P<0.05),其中硫辛酸组小鼠总移动距离、平均运动速度、悬线实验评分高于模型组,低于对照组;而下落潜伏期高于对照组,低于模型组(P<0.05)。3组小鼠脑组织神经元凋亡率差异有统计学意义(P<0.05),其中硫辛酸组神经元凋亡率明显低于模型组,高于对照组(P<0.05)。3组小鼠纹状体DA、DOPAC以及SIRT1、P53表达水平差异有统计学意义(P<0.05),其中硫辛酸组小鼠DA、DOPAC、SIRT1表达水平明显高于模型组,低于对照组(P<0.05),而P53表达水平低于模型组,高于对照组(P<0.05)。结论硫辛酸可减轻PD动物模型小鼠神经元凋亡情况,从而发挥神经保护作用,其作用机制可能与上调SIRT1/P53通路有关。Objective To study the neuroprotective effect of lipoic acid regulating silent information regulator 1(SIRT1)/P53 pathway on Parkinson's disease(PD)animal models.Methods Forty-five male C517BL/6J mice were randomly divided into three groups:control group,model group and lipoic acid group.Both the model group and the lipoic acid group were induced to establish PD mouse models by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).The lipoic acid group was given intraperitoneal injection of lipoic acid,the model group and control group were intraperitoneally injected with an equal volume of normal saline.The ultrastructure of the midbrain neurons in the three groups of mice was observed under electron microscope,and the effect of lipoic acid on motor deficits in Parkinson's mice was evaluated by rope test,open field test and rotarod test.The apoptosis of dopaminergic neurons in the striatum and the expression levels of DA and DOPAC were evaluated.Western blotting was used to detect the expression of SIRT1/P53 pathway-related proteins.Results There were statistically significant differences in the total moving distance,average moving speed,hanging wire test score and falling latency of the three groups of mice(P<0.05).The score was higher than that of the model group and lower than that of the control group,while the fall latency was higher than that of the control group and lower than that of the model group(P<0.05).There were statistically significant differences in the neuron apoptosis rate in the brain tissue of the three groups of mice(P<0.05).The neuron apoptosis rate in the lipoic acid group was significantly lower than that in the model group and higher than that in the control group(P<0.05).There were statistically significant differences in the expression levels of DA,DOPAC,SIRT1 and P53 in the striatum of the three groups of mice(P<0.05),and the expression levels of DA,DOPAC and SIRT1 in the lipoic acid group were significantly higher than those in the model group and lower than those in the control group(

关 键 词：帕金森病 硫辛酸 SIRT1/P53通路 神经保护 纹状体 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]