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背景与目的:观察醋酸铅对发育期大鼠海马区细胞凋亡及其相关基因XIAP和SmacmRNA表达的影响,以揭示铅的神经毒作用机制。材料与方法:48只健康雄性1月龄SD大鼠,被随机分为:对照组(给予双蒸水灌胃6周),实验组分别按低、中、高剂量,依次给予2、20、200mg/kg醋酸铅溶液灌胃6周。以石墨炉原子吸收法测血铅浓度;用TUNEL法检测大鼠脑组织细胞凋亡的发生情况;用RT_PCR检测海马细胞XIAP和SmacmRNA的表达。结果:大鼠血液中的铅浓度随染铅浓度的增加而升高(P<0.01)。各醋酸铅剂量组大鼠海马组织凋亡细胞数量明显增加,其凋亡指数显著高于对照组(P<0.01),并且随染铅浓度的上升而增加;大鼠海马组织的XIAP基因表达有下降趋势,高铅剂量组显著低于对照组(P<0.01)。相关分析显示XIAP基因表达水平与血铅浓度呈负相关。各组大鼠海马组织的Smac基因表达水平无明显差别,和血铅浓度也无相关性(P均<0.05)。结论:铅可诱导发育期大鼠的海马细胞凋亡率上升,该现象可能是通过抑制细胞XIAP基因的表达来发挥作用的。
BACKGROUND & AIM: To observe the effects of lead acetate on the apoptosis of hippocampus and the expression of XIAP and SmacmRNA in hippocampus of developing rats to reveal the mechanism of lead toxicity. MATERIALS AND METHODS: Forty-eight healthy 1-month-old male Sprague-Dawley rats were randomly divided into control group (given with double distilled water for 6 weeks), the experimental group were given low, medium and high dose, 200mg / kg lead acetate solution for 6 weeks. The levels of lead in blood were measured by graphite furnace atomic absorption spectrometry. The apoptosis of rat brain was detected by TUNEL method. The expressions of XIAP and SmacmRNA in hippocampal were detected by RT-PCR. Results: The concentration of lead in rat blood increased with the increase of lead concentration (P <0.01). The apoptotic index of hippocampus in lead acetate group was significantly increased, and the apoptosis index was significantly higher than that in control group (P <0.01), and increased with the increase of lead concentration. The expression of XIAP gene in hippocampus decreased Trend, high lead dose group was significantly lower than the control group (P <0.01). Correlation analysis showed that the expression level of XIAP was negatively correlated with blood lead concentration. Smac gene expression levels in hippocampus of rats in each group showed no significant difference, and there was no correlation between Smac and blood lead (P <0.05). Conclusion: Lead can induce the apoptosis rate of hippocampus of developing rats, which may be through inhibiting the expression of XIAP gene in cells.