黄芩苷对黑质内注射三氯化铁所致中脑损毁的保护作用

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【摘要】  目的探讨黑质部位注射FeCl3制备帕金森病模型的可行性,并观察黄芩苷的保护作用。方法雄性Wistar大鼠,黄芩苷组术前灌胃黄芩苷(78 mg·kg1·d-1)1周;模型组和黄芩苷组均单侧黑质定向注射FeCl3(40μg)造摸,术后第5周中脑黑质病理切片行免疫组化分析酪氨酸羟化酶(TH);铁染色观察中脑黑质铁含量。结果①造模后2~3 d,动物头、身体向注射对侧倾斜,部分动物自发向注射对侧旋转,有些伴有抽搐和强直。术后7 d尚见有不同程度类帕金森病表现,震颤、弓背;黄芩苷组死亡率(模型组46%,黄芩苷组36%)降低。②注射侧中脑见明显的铁沉积,脑组织损毁严重。而黄芩苷组未见这一现象。③注射侧黑质多巴胺能神经细胞明显缺失。黄芩苷预防给药1周没能阻止这种损伤。结论铁剂黑质注射造成的中脑损毁严重,动物有类帕金森病表现。黄芩苷能阻止铁在中脑沉积及所造成的损毁,显示明显的保护作用。

【关键词】  三氯化铁; 帕金森病; 帕金森模型; 黄芩苷

    ChinaAbstract:ObjectiveTo explore the feasibility of developing Parkinson's disease model induced by injecting FeCl3 into nigrostriatum, and to observe the protective effect of baicalin on the model.MethodsThe Wistar rats of druggroup were administered baicalin (78mg·kg-1·d-1) by oral for 1 week. The FeCl3 (40μg) was injected into the unilateral substantia nigra (SN) on all rats. The dopamine neurons at the mesencephalon nigra were observed by tyrosine hydroxylase (TH)  immunohistochemistry in the 5th week after injection. The iron contents were measured by iron stain. Results①The head and body of animals was gradient toward side of the opposite injected mesencephalon after operated for 23 days, spontaneous rotation behaviors toward the opposite side of injected side and convuision and tetany for some rats. Some similar Parkinson's disease behavior appeared, such as thrill, hunchback on the 7th day after injection, mortality were reduced in rats of Baicalingroup rats. ②Iron deposit in the nigrostriatum and lesions of the mesencephalon appeared on injected side in the modelgroup, but it weren't in rats of Baicalingroup. ③The Nigrostriatal dopaminergic neurons were decreased on injected side and this decrease could not be prevented by Baicalin treatment prior 1 week.ConclusionThe lesion of the mesencephalon induced by FeCl3 injection is severe, and some similar Parkinson's disease behaviors can appeare.The results we report here offered support that the protective effect of baicalin on Iron gather and mesencephlalon lesion induced FeCl3 injection in rats.

  Key words: Parkinson's disease;Parkinson's disease model;Baicalin
   
  帕金森病(Parkinson's disease, PD) 是常见的神经退行性疾病。研究证明PD患者黑质内铁含量异常升高是帕金森病一个共有而不变的特征;不仅脑内铁代谢紊乱,流行病学调查还显示其全身铁代谢也遭到破坏[1]。研究提示铁直接参与PD的神经变性改变。铁代谢紊乱、铁诱导的氧应激自由基生成增加是PD发病中的重要环节,与导致PD患者氧化应激状态及黑质损伤密切有关。铁螯合剂在动物实验中显示出显著的疗效,动物在用6OHDA处理之前给予铁螯合剂去铁胺可明显减轻6OHDA诱发的黑质多巴胺能神经变性[2]。铁螯合剂在治疗PD中的潜能使它已成为寻找抗PD新药关注的方向之一。

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