目的研究铅暴露对不同生长阶段SD雄性大鼠脑组织铅、铁水平及DNA氧化损伤的影响。方法将12只SPF级SD雌性大鼠随机分为3组,分别为空白对照(去离子水)组和低(0.8g/L)、高(1.5g/L)剂量乙酸铅染毒组,每组4只。采用自由饮水方式进行染毒,自妊娠前10d至仔鼠断乳(出生后21d)。待断乳后,每组选取21只雄性仔鼠,相应各组分别自由饮用去离子水和0-3、0.9g/L乙酸铅溶液。仔鼠分别饲养至断乳(21d)、中年(12个月)、老年(18个月)时,检测脑组织中铅、铁和8一羟基脱氧鸟苷(8-hydroxy-2’-deoxyguanosine,8-OHdG)的水平。结果在同一生长阶段,随着铅染毒剂量的升高,大鼠脑铅、脑铁及脑组织8-OHdG水平均增加。线性回归分析结果显示,在断乳期和老年期,大鼠脑铁、脑8-OHdG水平随着脑铅水平的升高而上升(P〈0.05);同时,脑铅、脑铁联合作用使大鼠脑8-OHdG水平升高(P〈0.05)。而中年期无明显改变。在空白对照组和各剂量铅染毒组中,随着铅染毒时间的延长,大鼠脑铅、脑铁水平均增高(P〈0.05)。空白对照组中,脑8-OHdG水平在中年、老年期增高(P〈0.05);低剂量组改变不明显;高剂量组在老年期明显升高(P〈0.05),中年期改变不明显。结论铅暴露可致SD大鼠脑组织铁过载及DNA氧化损伤。
Objective To investigate the brain iron,brain DNA and oxidative stress of the SD rat brain in different development stages. Methods SPF female and male Sprague-Dawley rats were respectively randomly divided into three groups:control,low lead-exposed, high lead-exposed. Lead-exposed female rats drank 0.8,1.5 g/L lead acetate solutions during the first ten-day of pregnancy until weaning and then the male pups received 0.3,0.9 g/L lead acetate solution depending on their group. When pups grew up to weaning (21 days),mid-age (ten months) and old-age (18 months) , the DNA of brain tissue were extracted,digested and the contents of 8-OHdG were determined by ELISA. The offspring were measured the lead and iron concentration of brain by ICP-AES. Results At the same growth stage,the brain lead, brain iron and 8-OHdG contents were higher in different lead exposure groups compared with the control. Linear regression showed that the brain iron and the 8-OHdG contents of the brain were higher in different lead exposure groups (P〈0.05); Brain iron and brain lead could jointly raise the 8-OHdG of brain(P〈0.05), whether a synergistic effect between brain iron and brain lead needed to be validated. The 8-OHdG contents increased with lead exposure levels at weaning and the old-age (P〈0.05). In control group,the mid-age and old-age groups were higher than the weaning rats (P〈0.05). In high lead group, the old-age group was higher than the mid-age and weaning rats (P〈O.05). There was no significant difference in mid-aged rats. Conclusion Lead exposure may induce iron overload and DNA damage in rat brain.