铁剂诱发黑质多巴胺能神经元变性  

Iron induces the degeneration of nigral dopaminergic neurons in rats

作　　者：陈先文[1] 陈生弟[1] 刘振国[1] 肖勤[1] 王瑛[1] 翁中芳[1] 

机构地区：[1]上海第二医科大学附属瑞金医院神经科帕金森病诊疗与研究中心,200025

出　　处：《中华老年医学杂志》2002年第1期44-47,共4页Chinese Journal of Geriatrics

基　　金：国家重点基础研究规划资助项目 (G19990 5 40 0 8) ;上海市卫生系统百名跨世纪优秀学科带头人培养计划资助项目( 97BR0 0 1) ;上海市科委青年科技"启明星后"计划资助项目( 97QMB14 10 )

摘　　要：目的　探讨铁剂对黑质多巴胺 (DA)能神经元的毒性作用 ,为阐明帕金森病 (PD)发病机制提供资料。　方法　将铁剂定向注射至大鼠一侧黑质 ,6周后通过酪氨酸羟化酶 (TH)免疫组化染色观察黑质DA能神经元的损伤情况 ,高压液相色谱 电化学法 (HPLC ECD)检测DA及其代谢产物含量 ,化学分光比色法检测中脑自由基代谢变化。　结果　大剂量铁剂 (4 0 μg)可诱发大鼠黑质TH阳性细胞显著变性、丢失 ,纹状体DA及其代谢产物含量显著降低 ,中脑脂质过氧化产物丙二醛 (MDA)升高、谷胱甘肽 (GSH)含量降低。小剂量铁剂 (4 μg)无明显致TH阳性细胞丢失作用 ,但也可使中脑MDA升高。　结论　铁剂可造成中脑黑质DA能神经元变性丢失 ,铁介导的自由基生成增加在PD发病过程中起重要作用。Objective To explore the toxic effects of iron on nigral dopaminergic(DA) neurons and provide the data for elucidating the pathogenesis of Parkinson's disease. Methods Iron was stereotaxically infused into right substantia nigra(SN). Tyrosine hydroxylase(TH)-positive cells in the substantia nigra were examined by immunohistochemical assay and the contents of DA and its metabolites in the striatum were measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD) 6 weeks later. Free radical metabolism in the midbrain was also examined by chemical spectrophotometry. Results Infusions of high dose iron(40 μg) induced significant degeneration and loss of TH positive cells in the pars compacta of SN, marked reduction of striatal DA and its metabolites, and elevated lipid peroxidative products and decreased glutathione. Infusion of low dose iron(4 μg) also induced lipid peroxidation, but did not produce significant loss of TH positive cells in the pars compacta of SN. Conclusions Excess iron could induce the degeneration of nigral DA neurons; iron-mediated freeradical synthesis might play an important role in the pathogenesis of Parkinson's disease.

关 键 词：神经变性 帕金森病 自由基 铁剂 DA 

分 类 号：R742[医药卫生—神经病学与精神病学]