姜黄素对帕金森病小鼠模型黑质多巴胺能神经元损伤的保护作用

目的研究姜黄素对由MPTP诱发的帕金森病小鼠模型的脑保护作用及其可能机制。方法应用免疫组织化学染色法和蛋白质印迹法(Western blotting)分别观察姜黄素干预前后帕金森病小鼠中脑黑质-纹状体系统中酪氨酸羟化酶、胶质纤维酸性蛋白阳性神经元数目的变化,以及酪氨酸羟化酶、诱导型一氧化氮合酶和胶质纤维酸性蛋白表达水平的变化。结果MPTP组小鼠中脑黑质酪氨酸羟化酶和胶质纤维酸性蛋白阳性神经元数目明显减少,与正常对照组及治疗组相比差异有统计学意义(均P<0.05)。经不同剂量(5mg/kg、50mg/kg和150mg/kg)的姜黄素干预治疗后,小鼠中脑纹状体中的酪氨酸羟化酶蛋白表达水平(相对灰度值)明显升高,而黑质中诱导型一氧化氮合酶和胶质纤维酸性蛋白表达水平明显降低,与MPTP组比较差异均有统计学意义(P<0.05);MPTP组与溶剂对照组(MPTP DMSO)之间差异无统计学意义(P>0.05)。结论姜黄素可以有效地拮抗MPTP诱导的帕金森病小鼠模型黑质多巴胺能神经元的丢失,其机制可能与姜黄素降低黑质多巴胺能神经元活性氧含量以及抑制炎症反应等作用有关。

The protection of curcumin in nigral dopaminergic neuronal injury of mice model of Parkinson disease

Objective To investigate the neuroprotective effects of curcumin on dopaminergic neuronal injury of parkinsonian mice model induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Methods The C57BL mice were divided into 4 groups: MPTP group, MPTP curcumin group, saline control group and solvent control (MPTP DMSO) group. The number of tyrosine hydroxylase (TH) positive neurons and glial fibrillary acidic protein (GFAP) positive neurons in substantia nigra-striatum system was measured by immunohistochemistry. The expression levels of TH, inducible nitric oxide synthase (iNOS) and GFAP in substantia nigra-striatum system were detected by Western blotting. Results The number of TH positive neurons and GFAP positive neurons in the substantia nigra was significantly reduced in MPTP group than that in MPTP curcumin and saline control groups (P < 0.05, for all). After different doses of curcumin treatment (5 mg/kg, 50 mg/kg and 150 mg/kg), TH expression level obviously increased in striatum, and iNOS and GFAP expression levels markly decreased in subsfantia nigra, the differences with MPTP group were all significant (P < 0.05), but the differences between MPTP group and MPTP DMSO group were not siginifcant (P > 0.05). Conclusion Curcumin could effectively block the loss of dopaminergic neurons in the parkinsonian mice model induced by MPTP. The mechanism may be related to its antioxidantion and anti-inflammatory activities.