摘要
目的 探讨凋亡机制在 β 淀粉样蛋白 (Aβ)脑内致阿尔茨海默病 (AD)作用中的意义及褪黑素 (MT)对Aβ脑内神经毒性的干预效果。方法 将Aβ1 4 0 微量注射至大鼠右侧海马CA1区 ,7d后 ,用尼氏染色检测神经元丢失 ,HE染色、TUNEL染色及透射电镜检测细胞凋亡 ;用免疫组化SABC法检测Bax/Bcl 2的表达。结果 Aβ组右侧海马CA1区发现大量凋亡细胞 ,而假手术对照组和生理盐水对照组未发现细胞凋亡 ;Aβ组Bax表达增强 ,而Bcl 2表达在上述三组间无明显差异 ;MT组海马CA1区神经元计数为 47.4± 5 .9,明显多于Aβ组 (2 9.4± 4.5 ) ,但少于生理盐水对照组 (79.8± 7.6 )和假手术对照组 (83.1± 8.5 ) ,MT组细胞凋亡 (8.4± 3.7)少于Aβ组 (18.9± 6 .1)。 结论 Aβ能诱导脑内神经元凋亡 ,并可能与促进Bax的表达有关 ;MT能明显减轻Aβ的脑内神经毒性 。
Objective To investigate both the role of apoptosis in the pathogenesis of Aβ and the therapeutic effect of melatonin on the neurotoxicity of Aβ in the rat brains. Methods Aβ 1-40 was microinjected into CA1 subfield in the right hippocampus of rats.Seven days later, apoptosis of the neurons was determined with the use of Nissl staining, hematoxylin eosin staining,TUNEL staining and transmission electron microscopy(TEM).The expression of Bax/Bcl 2 was determined with immunohistochemistry SABC method. Results In the Aβ group, hematoxylin eosin staining showed many neurons in the CA1 subfied cell bodies became shrunken,whereas the chromatin were condensed and deeply stained. TUNEL staining indicated that lots of cells with nuclei brown yellow stained and ringed. The TEM examination revealed compact patches or rings or cells like crescent moons with condensed nuclear chromatin but with no apparent nuclear membrane disruption. In comparision with the control groups,the expression of the Bax in the hippocampal CA1 subfields in the Aβ group was stronger,but the expression of Bcl 2 showed no obvious difference among the above three groups. The numbers of the neurons in the hippocampal CA1 subfields in the melatoin group were 47.4±5.9,more than in the Aβ group (29.4± 4.5), but less than in the normal saline control group (79.8±7.6)or in the sham operation control group (83.1±8.5). Apoptotic cells in the melatonin group (8.4±3.7)were less than in the Aβ group (18.9±6.1). Conclusions The result of this study indicated that Aβ could induce the neuronal apoptosis in the rat brains, and the stronger expression of Bax might play an important role in those neuronal apoptosis, whereas, melatonin could markedly inhibit the neurotoxicity of Aβ in the rat brains, which suggested that complementing of melatonin might be beneficial for the prevention and therapy of Alzheimer′s Disease.
出处
《中华神经科杂志》
CAS
CSCD
2000年第1期7-9,共3页
Chinese Journal of Neurology
