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目的探讨泛素-蛋白酶体系统关键酶泛素连接酶hHrd1在帕金森病动物模型中的表达,并探讨其意义。方法应用立体定向仪,经大鼠黑质和内侧前脑束两靶点微量注射6-羟多巴制作帕金森病模型,2周后阿扑吗啡腹腔注射,筛选成功模型。免疫组化检测泛素连接酶hHrd1在帕金森病模型大鼠中脑的表达,并行Western blot定量分析。结果注射6-羟多巴到黑质和内侧前脑束双靶点,通过大鼠旋转实验测试,造模成功率为57.9%。泛素连接酶hHrd1在帕金森病模型中呈高表达,且呈区域性,如黑质、红核、中缝核及缰内侧核呈强阳性。结论泛素连接酶hHrd1在帕金森病模型中高表达,揭示泛素-蛋白酶体系统功能异常与帕金森病发病过程有着极其密切的关系,可能成为帕金森病治疗的又一途径。
Objective To investigate the expression of ubiquitin-proteasome system key enzyme ubiquitin ligase hHrd1 in Parkinson’s disease animal model and to explore its significance. Methods The stereotaxic apparatus was used to produce Parkinson’s disease model by microinjection of 6-hydroxydopamine into the substantia nigra and medial forebrain. Two weeks later, apomorphine was injected intraperitoneally to screen the successful model. Immunohistochemistry was used to detect the expression of ubiquitin ligase hHrd1 in the midbrain of Parkinson’s disease rats and Western blot analysis. Results The target of 6-hydroxy-dopa injection to the substantia nigra and medial forebrain was double-target. The success rate of modeling was 57.9% through rat rotation test. Ubiquitin ligase hHrd1 in Parkinson’s disease model was highly expressed, and was regional, such as the substantia nigra, the red nucleus, the middle of the nucleus and the medial nucleus was strongly positive. Conclusions Ubiquitin ligase hHrd1 is highly expressed in Parkinson ’s disease model. It is revealed that the abnormal function of ubiquitin - proteasome system is closely related to the pathogenesis of Parkinson’ s disease and may be another way to treat Parkinson ’s disease.