6-羟多巴胺纹状体内注射制作大鼠帕金森病模型的研究

目的 为拓宽6-OHDA损毁多巴胺能神经元所制备大鼠帕金森病模型的应用范围，采用多位点纹状体内注入6-OHDA的途径来制备模型。方法 研究用SD大鼠，两个针道内四点定位注射，每点注射3μg／μ16-OHDA3μl。结果 术后两周出现缓慢旋转，4周旋转行为达到7转／分并保持稳定；形态学染色可见损毁1周后注射侧黑质酪氨酸羟化酶免疫组化阳性细胞减少20％，2周后减少38％，3～4周减少70％以上，6周后损伤趋缓。高效液相-电化学法活体检测纹状体内多巴胺的代谢产物3、4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)，发现注射侧和非注射侧相比含量分别下降98．33％和96．05％；组织匀浆检测损毁侧黑质多巴胺含量下降了73％以上，3、4-二羟基苯乙酸(DOPAC)含量下降60％。结论 纹状体内注射6-OHDA能够制备帕金森病大鼠模型。

ESTABLISHMENT OF RAT MODEL OF PARKINSON DISEASE BY INJECTING 6-HYDROXYDOPAMINE INTO STRIATUM

Objective To explore the establishment of a new rat model of Parkinson's disease by direct injection of 6-hydroxydopamine in the striatum. Method Sixty male SD rats were stereotaxically injected in the left striatum with 6-hydroxydopamine (6-OHDA)which was released slowly into the striatum in fourneedle sites. Result Slow rotations were recorded two weeks after injection, and rotations of about 7 times/min in seven of ten rats were recorded in the 4th week after injection. The immunohistochemical staining showed that the loss of TH-positive neurons did not appear until the 7th day in therats treated with 6-OHDA. A 38% reduction of TH-postive neurons in the lesion side was observed in weeks, and more than 70% in 3-4 weeks. Four weeks after the injection, the extracellular levels of dopamine metabolites (DOPAC, HVA) in the striatum of the rat model were measured by using intracerebral microdialysis, coupled with high performance liquid chromatography and electrochemical detection (HPLC-ED). The levels of DOPAC and HVA were decreased by 98.33% and 96.05% in the lesion side when compared with those in the contralateral side. Meanwhile the levels of DA and its metabolites in the homogenate of the striatum were also measured by HPLC-ED. Compared with the contralateral side,the levels of DA, DOPAC and HVA in the lesion side were decreased by 73% and 60%. Conclusion Intrastriatal 6-hydroxydopamine lesions can establish a rat model of Parkinson's disease.