3 种不同脑区定点注射 6-OHDA 单侧损伤大鼠帕金森病模型的比较研究

摘要] 目 的 从 神 经 行 为 学、组 织 病 理 和 生 化 方 面 对 3 种 不 同 脑 区 单 侧 定 点 注 射 6- 羟 基 多 巴 胺 ( 6- hydroxydopamine , 6-OHDA )损伤大鼠帕金森病( Parkinsondisease , PD )模型进行比较研究。方法 健康雄性 SD 大 鼠随机分为 3 组( n =10 ):纹状体组、黑质组、黑质 + 中脑腹侧被盖区组。根据脑立体定位图谱,将微量 6-OHDA 单点定位注入大鼠中脑黑质区、纹状体区和双点定位注入黑质区与中脑腹侧被盖区。观察阿朴吗啡诱发大鼠旋转 行为,免疫组织化学检测大鼠黑质区酪氨酸( tyrosinehydroxy-lase , TH + )阳性神经元数目,电化学高效液相色谱法 检测纹状体中多巴胺( dopamine , DA )及其代谢产物 3 , 4- 二羟苯乙酸( dihydroxy-phenylaceticacid , DOPAC )和高香 草酸( homovanillicacid , HVA )含量。结果 纹状体组 3 周后模型稳定,黑质组与黑质 + 中脑腹侧被盖区组大鼠 2 周后稳定, 3 组 30min 内向健侧转圈数均呈升高趋势,黑质 + 中脑腹侧被盖区组高于纹状体组和黑质组,组间· 时点间交互作用差异有统计学意义( P <0.05 )。纹状体组和黑质 + 中脑腹侧被盖区组造模成功率高于黑质组 ( P <0.05 )。 3 组大鼠注射 6-OHDA 损伤侧纹状体中 DA 、 DOPAC 、 HVA 含量和 TH + 神经元数目均明显低于非 损伤侧( P <0.05 )。结论 纹状体单点注射 6-OHDA 损伤建立 PD 模型成功率高,可作为研究 PD 的一种稳定可靠 的动物模型。

Comparative study of Parkinson disease rat model via unilateral injection of 6 OHDA into three different brain regions

［Abstract］ObjectiveTo compare Parkinson disease(PD) rat models via unilateral injection of 6 hydroxydopamine(6 OHDA) into three different brain regions from the aspects of neurobehavior, histopathology and biochemistry. MethodsHealthy male SD rats were randomly divided into three groups(n=10):striatum group， substantia nigra group，substantia nigra+ midbrain ventral tegmental area group. According to the stereotaxic atlas of the brain, the trace 6 OHDA unilateral injection into rat substantia nigra and striatum were performed via single point position in striatum group and in substantia nigra group, and 6 OHDA injection into rat substantia nigra and midbrain ventral tegmental area were performed by double point position in substantia nigra+midbrain ventral tegmental area group.The rotation behavior induced by apomorphine was observed in rats. The tyrosine positive neurons in the rat substantia nigra were detected by immunohistochemistry. The dopamine(DA) and its metabolic products 3, 4 dihydroxy phenyl acetic acid(DOPAC) and homovanillic acid(HVA) were measured by electrochemical high performance liquid phase chromatography in rat striatum. ResultsIn the rats with unilateral injection 6 OHDA into striatum viasingle point position, stablerotation appeared at 3 weeks, and a high rate of success in animal model was obtained. In the rats with substantia nigra injection model viasingle point and in the rats with substantia nigra + midbrain ventral tegmental area via double point position injection model, stable rotation appeared after 2 weeks, but animal model success rate is low. Three types of PD rat models in different brain regions injected by 6 OHDA showed that the number of tyrosinehydroxy lase neurons in substantia nigra area was severely deficient, and that the contents of DA and its metabolites(DOPAC, HVA) in striatum were significantly decreased. ConclusionRat model with unilateral injection 6 OHDA into striatum via single point position ishighly successful, which can be used as a stable and reliable animal model for the study on PD.