摘要
目的:观察synphilin-1 siRNA对6-羟多巴胺(6-hydroxydopamine,6-OHDA)诱导的帕金森病(PD)大鼠黑质多巴胺能神经元保护作用,从而探讨synphilin-1siRNA在帕金森病治疗中潜在的应用价值。方法:40只Wistar大鼠随机分成4组,假手术组、模型组s、iRNA组s、iRNA对照组,每组10只。模型组立体定向将6-OHDA注入左侧黑质制作PD模型,siRNA组s、iRNA对照组立体定向将synphilin-1siRNA、阴性对照synphilin-1 siRNA分别注入到各组大鼠的左侧黑质,然后用与第一组相同的方法注入6-OHDA,假手术组注入生理盐水作为对照组,术后2周用阿朴吗啡(APO)(0.5 mg/kg)诱发旋转,进行大鼠行为学检测。术后4周取大鼠的术侧中脑黑质利用免疫组化检测synphilin-1,酪氨酸羟化酶(TH)免疫阳性细胞(ir)的表达。结果:与假手术组比较,模型组synphilin-1-ir阳性细胞表达显著增加,而TH-ir阳性细胞显著减少;与模型组比较,siRNA组synphilin-1-ir阳性细胞表达显著减少,而TH-ir阳性细胞显著增加。结论:Synphilin-1在6-OHDA诱导的PD大鼠黑质神经元损伤机制中起一定作用,synphilin-1 siRNA具有神经保护作用,能为帕金森病的治疗提供新的思路和方法。
Objective： To explore the potential value of synphilin - 1 siRNA in 6 - hydroxydopamine （6 - OHDA） induced Parkinson＇s disease （PD）. Methods： Forty healthy male Wistar rats were divided into four groups randomly： the sham operation group, model group, siRNA group, siRNA negative control group, ten rats in each group. In model group： 6 - OHDA was stereotaxically injected in the left substantia nigra of rat. siRNA group and siRNA negative control group ： Synphilin - 1 siRNA and synphilin - 1 negative control siRNA were stereotaxically injected in the left substantia nigra twice respectively, and then 6 - OHDA was stereotaxically injected in the left substantia nigra with the same method as the model group. The sham operation group： Except for injection of same amount of normal saline containing 0.2 g/L antiscorbic acid, other managements of the sham - operated group were exactly same as the model group. Two weeks later, 0.5 mg/kg apomorphine （APO） was injected intraperitoneally to induce lateral rotation of the rats. Finally the behavior of rotation was tested. Four weeks after the operation, rats in each group were decapitated and midbrains were removed. The expression of synphilin - 1, tyrosine hydroxylase （TH） immunoreactive （ir） positive cells were tested in imunohistochemistry. Results ： Compared with the expression of synphilin - 1 - ir positive cells and TH - ir positive cells in sham operation group, the former increased, and the latter decreased significantly in model group; Compared with the expression of synphilin - 1 - ir positive cells and TH - ir positive cells in model group, the former decreased, and the latter increased significantly in siRNA group. Conclusion： Synphilin - 1 may play a role in protection in 6 - OHDA induced PD. Synphilin - 1 siRNA may has a neuroprotective effect which provides a new way for the treatment of PD.
出处
《长治医学院学报》
2009年第4期263-266,共4页
Journal of Changzhi Medical College
