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  

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

作　　者：李进[1] 孙杰[1] 赵楠[1] 吴钧[1] 刘俊[1] 马钢[1] 

机构地区：[1]云南省昆明市第一人民医院神经外科,云南昆明650011

出　　处：《河北医科大学学报》2016年第6期667-671,共5页Journal of Hebei Medical University

基　　金：云南省教育厅科学研究基金(2013C227)

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(Parkinson disease,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-phenyl acetic acid,DOPAC)和高香草酸(homovanillic acid,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。Objective To 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.Methods Healthy 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 trace6-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 3,4dihydroxy phenyl acetic acid（DOPAC）and homovanillic acid（HVA） were measured by electrochemical high-performance liquid phase chromatography in rat striatum.Results In the rats with unilateral injection 6-OHDA into striatum viasingle point position,stablerotation appeared at 3weeks,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 2weeks,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.Conclusion Rat model with unilateral injection 6-OHDA into striatum via single point position is highly successful,which can be used as a stable and reliable animal

关 键 词：帕金森病 羟基多巴胺类 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]