慢性镉中毒对小鼠学习记忆及海马CA3区的影响  

Effects of Chronic Cadmium Exposure on Learning,Memory and Hippocampus CA3 in Mice

作　　者：朱俊德[1] 余资江[1] 戈果[1] 康朝胜[1] 

机构地区：[1]贵阳医学院人体解剖学教研室,贵州贵阳550004

出　　处：《环境与健康杂志》2009年第7期576-579,F0003,共5页Journal of Environment and Health

基　　金：国家自然科学基金资助项目(30660189);贵阳医学院青年教师基金资助项目(K2007-61.67)

摘　　要：目的研究慢性镉中毒对小鼠学习记忆能力及海马CA3区神经元与星形胶质细胞的影响。方法将健康清洁级4～5月龄昆明小鼠20只随机分为对照组与镉中毒组,每组10只,雌雄各半。镉中毒组采用皮下注射2mg/kg氯化镉,每周2次,连续染毒3个月;对照组同时注射等体积生理盐水。染毒3个月后先对小鼠进行Y型迷宫学习记忆能力测试,并进行HE染色、尼氏染色、TUNEL与GFAP免疫组化染色光镜观察;并对海马CA3区神经元、凋亡神经元及GFAP免疫组化染色阳性神经元进行计数,测量GFAP阳性反应产物的平均光密度值。结果Y型迷宫检测结果显示,与对照组相比,镉中毒组小鼠的学习、记忆能力均降低,差异有统计学意义(P<0.05)。HE染色及尼氏染色结果显示,对照组小鼠海马CA3区神经元细胞排列整齐、规则、结构完整;镉中毒组小鼠海马CA3区部分神经元胞体变小,胞浆内可见大小、数量不等的嗜酸性颗粒,尼氏体明显减少或消失,有软化灶形成,并出现大量淋巴细胞浸润,而胶质细胞体积增大,数量增多。与对照组相比,镉中毒组海马CA3区神经元的数量较少,胶质细胞的数量较多,差异有统计学意义(P<0.05)。TUNEL免疫组化染色结果显示,对照组小鼠海马CA3区凋亡细胞皱缩,但质膜完整,细胞核、核仁消失,染色质呈颗粒状,边集于核膜下;镉中毒组小鼠海马CA3区凋亡细胞的细胞核染色质凝集成块,核固缩、颜色深、致密度高,进而核碎裂。对照组小鼠海马凋亡细胞数低于镉中毒组,差异有统计学意义(P<0.05)。GFAP免疫染色结果显示,对照组海马CA3区GFAP免疫染色阳性细胞较少,呈星形,胞浆内棕黄色反应颗粒较少,胞核不着色,位于细胞中央;镉中毒组海马CA3区GFAP免疫染色阳性细胞较多,胞浆内有丰富的棕黄色阳性反应颗粒,细胞胞体较大,突起多。与对照组相比,镉中毒组海马CA3区GFAP免疫染色阳性细胞数较多,胞Objective To study the learning and memory abilities together with the morphological changes in astrocyte and neuron in the hippoeampal CA3 area in mice induced by chronic cadmium exposure. Methods Twenty Kunming mice aged 4-5 months were selected by Y-maze and randomly divided into two groups. The cadmium exposed group treated with cadmium （CdCl2, 2 mg/kg） by subcutaneous injection, twice a week for 3 consecutive months, and the normal control group were injected with the equal dose of saline. The learning and memory abilities were detected by Y-maze after 3 months of treatment. The structure of astrocytes and neurons in CA3 area of hippocampus were observed under light microscope, and the quantitatively analysis was performed by cell morphometric technique. Results Compared with the control group,learning and memory capacity determined by Y-maze test in the cadmium exposed group were lower （P〈0.05）. HE and Nissl staining results showed that the neurons of the cadmium exposed group became smaller, karyopycnosis, reduced cytoplasm within ranging from the size and number of acidophilia granula, Nissl bodies were decreased significantly or even disappeared, and superficial coloration. Simultaneously, there were many different sizes softened focuses, and large number of lymphocytic infiltration in some regions;astrocytes were appeared volume augmentation and increased in number （P〈0.05）. Compared with the control group,the number of apoptosis cells of cadmium exposed group in hippocampus were increased （P〈0.05）. Compared with the control group, GFAP-positive cells and optical density in the cadmium exposed group significantly increased with a view of rich positive granules, spider shape,larger cell body, more processes with rough and long. Conclusion Chronic cadmium exposure can damage the learning and memory ability and cause the histopathological changes in hippocampal CA3 area with neurons decrease and astrocytes increase in mice.

关 键 词：金属 重 镉中毒 海马CA3区 神经元 学习记忆能力 星形胶质细胞 

分 类 号：R994.6[医药卫生—毒理学]