【摘要】 目的　探讨蛋白酶体在脑黑质变性和Lewy小体形成中的作用。　 方法　在大鼠单侧黑质致密部立体定向注射 0 2 μg、2 μg、8μg蛋白酶体抑制剂lactacystin ,对照组注射等量的生理盐水。观察大鼠自主行为和阿朴吗啡诱导的旋转行为 ;HE染色观察黑质变性和Lewy小体形态 ;应用免疫组化观察黑质细胞α synuclein和酪氨酸羟化酶 (TH)的表达 ;利用HPLC测定纹状体区多巴胺和高香草酸含量。　结果　注射lactacystin 0 2 μg组未见异常 ;注射 2 μg和 8μg组大鼠出现进行性的运动迟缓、少动、震颤、头向健侧倾斜 ;注射阿朴吗啡后 ,8μg组大鼠出现明显的向健侧旋转运动 ;给药后 3周 ,病理检查发现 2 μg和 8μg组大鼠黑质变性 ,部分黑质细胞内出现α synuclein免疫反应呈强阳性的嗜酸性包涵体 ;TH阳性细胞数分别减少了 6 8 2 4 % (P <0 0 5 )和 83 2 9% (P <0 0 1) ;纹状体区多巴胺、高香草酸含量分别减少了 6 9 6 3%、6 7 80 % (P <0 0 5 )和 81 5 4 %、85 6 2 % (P <0 0 1)。　结论　蛋白酶体功能障碍所引起的α synuclein降解受阻 ,是Lewy小体形成、黑质变性最终导致帕金森病的一个重要因素更多还原

【Abstract】 Objective To study the effect of proteasome on nigral degeneration and Lewy body formation. Methods By stereotaxic unilateral injection of different doses of lactacystin, a selective proteasome inhibitor, into the substantia nigral pars compacta of rats, the spontaneous and apomorphine induced contralateral behaviors of rats were observed. Nigral degeneration and Lewy body were viewed by HE staining; expressions of α synuclein and tyrosine hydroxylase in nigral cells were investigated by immunohistochemistry. Contents of dopamine and homovanillic acid were determined by HPLC. Results There were no difference between 0 2 μg group and control. Animals treated with 2 μg and 8 μg lactacystin developed progressively bradykinetic and displayed contralateral head tilting and tremor; apomorphine induced contralateral behavior was notably observed in rats of 8 μg group; 3 weeks later, nigral degeneration were present in 2 μg and 8 μg groups; some of nigral cells contained acidophilic Lewy body with intense immune response to α synuclein; the number of tyrosine hydroxylase positive cells in 2 μg and 8 μg groups were decreased by 68 24% ( P <0 05) and 83 29% ( P <0 01), respectively compared to control group; contents of dopamine and homovanillic acid in striatum of 2 μg and 8 μg groups were reduced by 69 63%, 67 80% ( P <0 05) and 81 54%, 85 62% ( P <0 01). Conclusions Failure of proteasome may play an important role in Lewy body formation and nigral degeneration.更多还原