摘要
目的:探讨蛋白酶体抑制剂lactacystin对大鼠纹状体多巴胺转运体(DAT)和囊泡单胺转运体2(VMAT2)蛋白表达的影响。方法:在大鼠单侧黑质致密部立体定向分别注射lactacystin0.2、2、8μg,对照组注射等量的生理盐水。观察大鼠自主行为和阿扑吗啡诱导旋转行为的变化;应用免疫组化观察黑质细胞α-synuclein和纹状体DAT和VMAT2蛋白表达。结果:注射lactacystin0.2μg组未见明显异常;2μg组和8μg组出现进行性的运动迟缓、少动、震颤、头向健侧倾斜;注射阿扑吗啡后,8μg组大鼠出现向健侧旋转运动。随着lactacystin剂量的增加,2μg组和8μg组黑质细胞α-synuclein的表达分别较对照组高出57%(P<0.01)和122%(P<0.001);纹状体DAT和VMAT2的表达分别较对照组减少了40%(P<0.01)、85%(P<0.001)和50%(P<0.01)和88%(P<0.001);DAT和VMAT2的比值分别较对照组高出了18%和32%。结论:Lactacystin可能通过抑制DAT和VMAT2的表达导致黑质细胞变性坏死及帕金森病的发生。
Aim ： To study the effect of lactacystin on dopamine ltransporter （DAT） and vesicular monoamine transporter （VMAT2） protein expressions in rats striatum. 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, expressions of alpha-synuclein in nigral cells and DAT and VMAT2 in striatum were investigated by immunohistochemistry. Results. There was no difference between 0.2 μg group and the 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, with the dose of lactacystin increasing, contents of α-synuclein were increased by 57%（P 〈 0.01）and 122% （P 〈 0.001）, contents of DAT and VMAT2 were decreased by 40%（P 〈 0.01）, 85%（P 〈 0.001）and 50% （P 〈 0.01）, 88% （P 〈 0.001）. Conclusion. Lactacystin may cause negral cells degeneration and Parkinson＇s disease by decreasing DAT and VMAT2 protein expressions.
出处
《中国临床神经科学》
2007年第2期143-147,共5页
Chinese Journal of Clinical Neurosciences
