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目的研究孕哺期铅暴露对成年仔鼠脑组织中DNA氧化损伤标志物8-羟基脱氧鸟苷(8-hydroxy deoxy guanosine,8-OHd G)、沉默信息调节因子1(silent information regulator 1,SIRT1)表达及学习记忆能力的影响。方法通过饮用2 g/L乙酸铅水溶液建立C57BL/6小鼠孕期染铅模型,并对哺乳期母鼠持续铅暴露至子代小鼠断乳,分娩3周后将仔鼠分笼以无铅去离子水饲养至12周龄,同时设立无染铅对照组。于仔鼠12周龄时以Morris水迷宫实验检测其学习记忆能力,以免疫组化方法检测8-OHd G在两组仔鼠脑组织中的表达和分布,采用Western blot测定其脑组织中SIRT1蛋白的表达水平。结果水迷宫实验结果显示,第3~5天铅暴露组成年仔鼠在定位航行实验中的平均逃避潜伏期长于对照组,最后一天穿越平台次数及在目标象限停留时间低于对照组,差异均有统计学意义(P<0.05)。铅暴露组仔鼠海马组织CA1区8-OHd G表达水平高于对照组,差异有统计学意义(P<0.05),但大脑皮层8-OHd G表达水平无明显差异(P>0.05)。铅暴露仔鼠脑组织胞核内SIRT1水平低于对照组,胞浆内SIRT1水平高于对照组,差异均有统计学意义(P<0.05)。结论孕哺期铅暴露对成年仔鼠学习记忆能力的影响可能与脑组织(特别是海马组织)DNA氧化损伤有关;铅暴露使成年仔鼠脑组织中SIRT1发生核质转移,该现象可能与SIRT1对铅暴露小鼠的神经保护作用有关。
Objective To investigate the effects of lead exposure during pregnancy and lactation on the expression of 8-hydroxydeoxy guanosine (8-OHdG), silent information regulator 1 (SIRT1) ) Expression and learning and memory ability. Methods The model of lead exposure in C57BL / 6 mice during pregnancy was established by drinking 2 g / L lead acetate aqueous solution. Continuous exposure of lead to the offspring of the offspring in lactating mothers was performed. After 3 weeks of delivery, Deionized water to 12 weeks of age, while establishing a lead-free control group. At 12 weeks of age, Morris water maze test was used to detect the learning and memory abilities. The expression and distribution of 8-OHd G in the brains of the two groups were detected by immunohistochemistry. The levels of SIRT1 Protein expression levels. Results The results of water maze test showed that on the 3rd to 5th days of exposure, the average escape latency of the offspring of lead exposure in experimental group was longer than that of the control group, the number of passing platform on the last day and the retention time in the target quadrant were lower than those in the control group Statistical significance (P <0.05). The expression level of 8-OHd G in hippocampus CA1 of lead exposed group was higher than that of control group (P <0.05), but the expression of 8-OHd G in cerebral cortex had no significant difference (P> 0.05). The levels of SIRT1 in the brain of lead exposed offspring rats were lower than those in the control group, and the intracytoplasmic SIRT1 levels were higher than those in the control group (P <0.05). Conclusion The effects of lead exposure during pregnancy and lactation on the learning and memory abilities of adult offspring may be related to DNA oxidative damage in brain tissue (especially in hippocampus). Lead exposure may induce nuclear transfer of SIRT1 in adult offspring rats, which may be related to SIRT1 On the lead-exposed mice neuroprotective effects.