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脑脊液高浓度铁诱导大鼠阿尔茨海默病样行为学和病理学的特征性变化

Behavioral and Pathological Changes Characteristic of Alzheimer’s Disease Induced by High Iron Concentration in the Cerebrospinal Fluid in Rats

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【作者】 李琳张志华吴建梁靳峥

【Author】 LI Lin, ZHANG Zhi hua, WU Jian liang, JIN Zheng( Institute of Geratology, Shanxi Medical University, Taiyuan 030001, China )

【机构】 山西医科大学老年医学研究所山西医科大学老年医学研究所 太原030001太原030001太原030001

【摘要】 目的 研究大鼠脑脊液铁离子浓度增高诱导的阿尔茨海默病(AD)样行为学、病理学特征性变化。方法 16只Wistar大鼠随机分为实验组和对照组,两组大鼠给予苯巴比妥 40mg·kg 1,ip,大鼠麻醉后,实验组 10只大鼠给予含三氯化铁 52μg·μL 1的人工脑脊液 10μL,icv,对照组 6只大鼠给予等体积的人工脑脊液,icv,第 5, 10天重复注射。用Marri水迷宫测定行为学改变,流式细胞仪检测凋亡细胞,免疫组织化学方法染色Aβ免疫斑块,透射电镜下观察超微结构变化。结果 实验组大鼠平均逃避潜伏时间为 (34 67±2 82)s,对照组为 (17 79±2 04)s(P<0 01),实验组大鼠平均逃避潜伏距离 ( 1 122 00±3 34 )cm,对照组为 ( 617 00±2 51 )cm(P< 0 01 )。实验组凋亡细胞为 ( 14 27±0 40)%,对照组为(3 20±0 19)% (P<0. 01)。淡褐色的Aβ免疫斑块广泛散布于实验组大鼠的大脑皮质和海马区。实验组大鼠神经元突起空泡变性,并伴有线粒体变性形成的致密体。结论 大脑局部铁浓度增高可引起AD样行为学和病理学特征性改变。

【Abstract】 Objective To study the behavioral and pathological changes characteristic of Alzhemier’s disease (AD) induced by high iron concentration in the cerebrospinal fluid in rats. Methods 16 adult Wistar rats were randomly divided into the test group ( n =10) and the control group( n =6). Rats of both groups were anesthetized by giving an intraperitoneal injection of 40 mg·kg 1 of pentobarbital to each animal. 10 rats of the test group were then given each an injection of 10 μL of artificial cerebrospinal fluid(CSF) containing 52 μg·μL 1 of ferric chloride into the lateral ventricles of the brain. Rats of the control group were given each an injection of 10 μL of artificial CSF via the same route. These injections were repeated on the fifth and tenth days. Behavioral changes were assayed with the Morris water maze test. Apoptotic cells of the murine cerebral cortex were detected with flow cytometry, Aβ immune plaques stained with immunohistochemical methods and ultrastructural changes examined by transmission electron microscopy. Results The average times for rats of the test group and control group to reach the platform were (34.67±2.82 ) s and (17.79±2.04)s, respectively ( P <0.01). The average distances for rats of the test group and control group to reach the platform were (1 122.00±3.24) cm and (617.00±2.51) cm , respectively ( P <0.01). The percentages of apoptotic cells from rats of the test group and control group were (14.27±0.40) % and (3.20±0.19) %, respectively( P <0.01). Light brown coloured Aβ immune plaques were seen widely interspersed in the cerebral cortex and hippocampus of rats of the test group. Vacuolar degeneration of neuronal processes accompanied by dense bodies formed as a result of mitochondria degeneration was shown in the brain of the rats of the test group. Conclusion Behavioral and pathological changes characteristic of AD were induced in rats by high iron concentration in the cerebrospinal fluid in rats.

【基金】 国家归国人员基金资助项目 (基金编号:99 57)
  • 【文献出处】 医药导报 ,Herald of Medicine , 编辑部邮箱 ,2005年04期
  • 【分类号】R749.1
  • 【被引频次】2
  • 【下载频次】108
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