左旋多巴诱发异动症大鼠黑质胶质细胞变化的实验研究  

Experimental Study on the Changes of glial cells in the substantia nigra pars compacts of the Levodopa-induced dyskinesia rats

作　　者：龚道恺[1] 孙圣刚[2] 曹学兵[2] 

机构地区：[1]华中科技大学同济医学院附属荆州医院神经内科,434020 [2]华中科技大学同济医学院附属协和医院神经科

出　　处：《脑与神经疾病杂志》2006年第1期38-40,26,共4页Journal of Brain and Nervous Diseases

摘　　要：目的研究异动症(LID)大鼠黑质致密部(SNpc)胶质细胞的变化。方法6-羟多巴胺(6-OHDA)立体定位注射制备偏侧帕金森病(PD)大鼠模型,复方左旋多巴(L-dopa)甲酯腹腔内注射治疗4周(10mg.kg-1.d-1,每日2次)诱发异动症大鼠模型。采用免疫组化方法观察大鼠黑质致密部酪氨酸羟化酶(TH)、胶质纤维酸性蛋白(GFAP)、增殖细胞核抗原(PCNA)和S-100蛋白免疫阳性细胞的面密度进行定量分析。结果免疫组化方法证实,PD组、LID组和非LID组大鼠毁损侧SNpc部位的TH免疫阳性面密度较正常组大鼠明显减少(P<0.01),而GFAP、PCNA、S-100免疫阳性面密度则明显增多(P<0.01);LID组和PD组、非LID组相比较,SNpc部位TH的表达进一步减少(P<0.05),GFAP、PCNA、S-100的表达则进一步增加(P<0.05)。结论PD大鼠毁损侧SNpc部位存在明显的胶质细胞增生。LID大鼠毁损侧SNpc部位的多巴胺(DA)能神经元变性及胶质细胞增生较非LID大鼠及PD大鼠更为明显。我们推测SNpc部位的胶质细胞通过其对DA能神经元的神经保护和神经破坏的双重作用,间接影响着LID的发生及其严重程度。Objective： To study the changes of glial ceils in the substantia nigra pars compacts of the levodopa-induced dyskinesia rats. Methods： The hemiparkinsonian rat models were established with unilateral intraigral injection of 6- hydroxydopamine, then hemiparkinsonian rats received intraperitoneal injection of levodopa methylester / benserazide （10mg/kg/d） twice a day for 4 weeks to prepare LID rat model. Immunoeytochemistry was carried out to measure the changes of the expression of tyrosine hydroxylase, glial fibrillary acidic protein, proliferating cell nuclear antigen and 100 in the substantia nigra pars eompacta. Results： Compared with the control group, the dimension density of TH immunopositive granule in the SNpc of PD, LID and non LID group decreased significantly （P〈0.01）, while the dimension density of GFAP, PCNA and S-100 immunopositive granule increased in this area （P〈0.01）. The TH positive dimension densities on the lesioned side in LID group were significantly higher than those in the regions on the intact side. Conclusions： The glial cells in the lesioned SNpc of the hemiparkinsonian rats showed obviously increased activation. This activation of the rats in LID group was significantiy ineresed than rats in PD and non-LID groups. It suggested that glial cells in the SNpc could influence the occurrence and severity of LID indirectly.

关 键 词：左旋多巴 帕金森病 异常不自主运动 异动症 小胶质细胞 星形胶质细胞 

分 类 号：R742.5[医药卫生—神经病学与精神病学]