Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Cell Mol Neurobiol. 2010 Jul;30(5):769-74. doi: 10.1007/s10571-010-9504-1. Epub 2010 Feb 11.
Despite reduction in environmental lead, chronic lead exposure still possess a public health hazard, particularly in children, with devastating effects on developing CNS. To investigate the mechanism of this neurotoxicity, young and adult rats were used to study whether exposure to 500 ppm concentrations of lead could induce apoptosis in hippocampus. 2-4 and 12-14-week-old rats received lead acetate in concentration of 500 ppm for 40 days. Control animals received deionized distilled water. In lead-treated groups, the blood lead levels were increased by 3-4 folds. Light and electron microscopical study of hippocampus revealed increased apoptotic cells. Western blot analysis of Bax and Bcl-2 (pro- and anti-apoptotic gene products, respectively) indicated higher expression of Bax protein and no significant change in bcl-2 expression and accordingly increased the Bax/Bcl-2 ratio compared to control group, confirming the histological study. In conclusion, these data suggest that neurotoxicity of chronic lead exposure in hippocampus in vivo may partly be due to facilitation of apoptosis.
尽管环境中的铅含量有所降低，但慢性铅暴露仍然对公共健康构成危害，尤其是对儿童，对发育中的中枢神经系统有毁灭性影响。为了研究这种神经毒性的机制，我们使用年轻和成年大鼠来研究暴露于 500ppm 浓度的铅是否会导致海马体中的细胞凋亡。2-4 周龄和 12-14 周龄的大鼠接受 500ppm 的醋酸铅处理 40 天。对照组动物接受去离子蒸馏水。在铅处理组中，血液中的铅含量增加了 3-4 倍。海马体的光镜和电镜研究显示凋亡细胞增加。Bax 和 Bcl-2（分别为促凋亡和抗凋亡基因产物）的 Western blot 分析表明，Bax 蛋白表达增加，而 bcl-2 表达无明显变化，因此与对照组相比，Bax/Bcl-2 比值增加，证实了组织学研究。总之，这些数据表明，体内慢性铅暴露引起的海马体神经毒性可能部分是由于促进了细胞凋亡。
