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目的研究3-硝基丙酸(3-NP)多次预处理治疗帕金森病及其可能的机制。方法选择 C57BL小鼠,应用3-NP(20 mg/kg体重)腹腔注射进行预处理后,经腹腔注射MPTP(30 mg/kg体重)制造帕金森病模型,对小鼠进行动作行为评分;测定中脑黑质丙二醛(MDA)及还原型谷胱甘肽(GSH)含量。结果经腹腔注射MPTP后,小鼠爬杆实验、悬挂实验评分由对照组(2．7±0．1)分和(2．7±0．2)分下降至(1．0±0．4) 分和(0．9±0．2)分(P<0．01);经过3-NP单或多次预处理后,其评分明显上升(1．5±0．3,1．5±0．1;2．1± 0．5,2．3±0．3),差异均有统计学意义(P<0．05,P<0．01);多次预处理组与单次预处理组间差异也有统计学意义(P<0．05)。腹腔注射MPTP后MDA含量(5．39±0．68)μmol/g较对照组(2．33±0．12)μmol/g明显升高,差异有统计学意义(P<0．01);3-NP单次预处理后,MDA含量明显下降至(4．12±0．56)μmol/g,与MPTP 组比较,差异有统计学意义(P<0．05);3-NP多次预处理后,MDA含量下降更为明显(3．11±0．49)μmol/g,与 MPTP组比较,差异有统计学意义(P<0．01);多次预处理组与单次预处理组比较,差异也有统计学意义(P< 0．05);MPTP组GSH含量(2．46±0．47)mg/g较对照组(5．23±0．64)mg/g明显下降,差异有统计学意义(P <0．01),单次预处理后,GSH含量升高不明显(2．69±0．41)mg/g(P>0．05),多次预处理后GSH含量明显升高(3．95±0．33)mg/g,差异有统计学意义(P<0．05)。结论 3-NP多次预处理可通过减少MDA生成,激发 GSH合成,达到治疗帕金森病,保护多巴胺神经元的作用。
Objective To study the multi-pretreatment of 3-nitropropionic acid (3-NP) for the treatment of Parkinson’s disease and its possible mechanism. Methods C57BL mice were pretreated by intraperitoneal injection of 3-NP (20 mg / kg body weight) and then intraperitoneally injected with MPTP (30 mg / kg body weight) to make a model of Parkinson’s disease. The behavioral score of the mice was measured. Midbrain substantia nigra malondialdehyde (MDA) and reduced glutathione (GSH) content. Results After MPTP was administered intraperitoneally, the score of hanging experiment and hanging experiment decreased from (2.7 ± 0.1) and (2.7 ± 0.2) to (1.0 ± 0.4 ) And (0.9 ± 0.2) points (P <0.01). After single or multiple pretreatment with 3-NP, the score increased significantly (1.5 ± 0.3 and 1.5 ± 0.1, 0.5, 2.3 ± 0.3), the differences were statistically significant (P <0.05, P <0.01); multiple pretreatment group and single pre- There was also a statistically significant difference between treatment groups (P <0.05). After intraperitoneal injection of MPTP, the content of MDA (5.39 ± 0.68) μmol / g was significantly higher than that of the control group (2.33 ± 0.12) μmol / g, the difference was statistically significant (P <0.01). Compared with MPTP group, the content of MDA significantly decreased to (4.12 ± 0.56) μmol / g after 3-NP pretreatment, the difference was statistically significant (P <0.05) Compared with MPTP group, the content of MDA decreased more significantly (3.11 ± 0.49) μmol / g after pretreatment (P <0.01) (P <0.05). GSH level in MPTP group (2.46 ± 0.47) mg / g was significantly lower than that in control group (5.23 ± 0.64) mg / g , The difference was statistically significant (P <0.01). After single pretreatment, the GSH content was not significantly increased (2.69 ± 0.41) mg / g (P> 0.05) After GSH content was significantly increased (3.95 ± 0.33) mg / g, the difference was statistically significant (P <0.05). Conclusions 3-NP multiple pretreatment can reduce GSH production and stimulate GSH synthesis to protect Parkinson’s disease and protect dopamine neurons.