苦参碱对MPTP诱导帕金森多巴胺能神经元损伤的保护作用  

Protective Effect of Matrine on Dopaminergic Neuron Injury in MPTP-induced Parkinson's Disease

作　　者：孟繁华[1] 范振崴[2] Meng Fanhua;Fan Zhenwei(Affiliated Hospital of Beihua University,Jilin 132011,China;Nursing College of Beihua University,Jilin 132013,China)

机构地区：[1]北华大学附属医院,吉林吉林132011 [2]北华大学护理学院,吉林吉林132013

出　　处：《北华大学学报（自然科学版）》2018年第5期608-611,共4页Journal of Beihua University（Natural Science）

基　　金：吉林市科技计划项目(201339003)

摘　　要：目的观察苦参碱在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森(FD)小鼠中对多巴胺能神经元损伤的保护作用和机制.方法将25只C57BL雄性小鼠随机分为5组,由空白对照组(A组)、MPTP组(B组)和3种苦参碱(4,8和16 mg/kg)加MPTP治疗组(分别为C,D和E组)组成.记录攀岩测试和运动活动实验的结果.4 d后处死小鼠并进行解剖,检测超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的水平,应用免疫荧光分析酪氨酸羟化酶(TH)的水平,通过蛋白质印记分析腹侧中脑核因子红细胞2相关因子2(Nrf2)的水平.结果苦参碱可以缓解PD相关联的典型行为,且随着增加苦参碱浓度,症状明显减轻.PD小鼠具有较低的SOD和GSH活性,且苦参碱部分扭转了SOD和GSH活性的变化.使用苦参碱的小鼠出现较高TH水平和TH阳性细胞的表达,Nrf2在PD小鼠中脑腹侧表达显著下降,而苦参碱能够扭转这种现象.结论通过促进在中脑腹侧抗氧化应激相关的Nrf2信号通路,苦参碱可以抑制PD多巴胺能神经元的氧化损伤.Objective To observe the protective effect and mechanism of matrine on injury of dopaminergic neurons in Parkinson ＇s mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（ MPTP）.Method Twenty-five C57 BL male mice were randomly divided into five groups： control group（ group A）,MPTP group（ group B） and three matrines（ 4,8 and 16 mg/kg） plus MPTP. Treatment groups（ C,D and E group,respectively）. Record the results of rock climbing tests and exercise activity experiments. After 4 days,the mice were sacrificed and dissected. The expression levels of superoxide dismutase（ SOD） and glutathione（ GSH） were measured. The level of tyrosine hydroxylase（ TH） was analyzed by immunofluorescence. The level of nuclear factor erythroid 2-related factor 2（ Nrf2） was analyzed by Western blot. Results Matrine can relieve the typical behavior associated with PD,and increase the concentration of matrine,the symptoms are significantly reduced.PD mice have lower SOD and GSH activity,and matrine partially reverses the changes in SOD and GSH activity.Matrine-using mice exhibited higher TH levels and expression of TH-positive cells. The expression of Nrf2 in the ventral midbrain of PD mice was significantly decreased,and matrine can reverse this phenomenon.Conclusion Matrine can inhibit the oxidative damage of PD dopaminergic neurons by promoting the antioxidative stress-related Nrf2 signaling pathway in the ventral midbrain.

关 键 词：苦参碱 帕金森小鼠 多巴胺神经元 1-甲基-4-苯基-1 2 3 6-四氢吡啶 核因子红细胞2相关因子2 

分 类 号：R742.5[医药卫生—神经病学与精神病学]