饮水铅暴露对大鼠脑组织APE1表达的影响及与氧化应激的关系研究

摘要

目的 探讨饮水铅暴露对大鼠大脑皮质、小脑、海马组织中脱嘌呤脱嘧啶核酸内切酶1(APE1)表达的影响及其与氧化应激的关系.方法 40只刚断乳雄性SD大鼠按体质量随机区组法均分为5组,对照组自由饮用去离子水,4个铅暴露组分别饮用100、200、400和800 mg/L醋酸铅溶液,连续染毒60 d后,取大脑皮质、小脑和海马组织,测定各组的超氧化物歧化酶(SOD)活力、过氧化氢(H2O2)水平和丙二醛(MDA)含量,蛋白印迹法检测APE1蛋白在各组织中的表达.结果 铅暴露后,大脑皮质、小脑、海马中APE1蛋白表达水平均低于对照组,且随染铅剂量的升高呈逐渐下降趋势(P<0.05);随着染铅剂量的升高,大脑皮质、小脑和海马中的SOD活力基本呈下降趋势;而H2O2及MDA含量随染铅剂量的升高基本呈逐渐升高趋势,大脑皮质、小脑和海马组织的APE1蛋白表达水平与其SOD活力呈正相关(r分别为0.619、0.380、0.375,P<0.05),而与H2O2水平和MDA含量呈负相关(r分别为-0.472、-0.535、-0.436,-0.514、-0.486、-0.316,P<0.05).结论 饮水铅暴露可导致大鼠脑组织APE1蛋白表达水平改变,且此种改变与铅所致的氧化应激有关.%Objective To observe the effects of lead exposure through drinking water on the expression of APE1 pro-tein in cerebral cortex, cerebellum and hippocampus of rats and its relationship with oxidative stress. Methods Forty weaned male SD rats were randomly assigned to five groups (control group and four exposure groups) according to body weights of rats. Rats in control group were given deionized water as drinking water. Rats in four exposure groups were given 100 mg/L, 200 mg/L, 400 mg/L and 800 mg/L lead acetate solution for 60 days. The activity of superoxide dismutase (SOD), the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in cortex, cerebellum and hippocampus were mea-sured using kits. The protein level of APE1 in cortex, cerebellum and hippocampus were detected by Western blotting assay. Results After being exposed to lead, the APE1 protein levels were significantly decreased in cortex, cerebellum and hippo-campus (P<0.05). The protein level showed a trend of gradual decline with the increase of exposed lead (P<0.05). With the increase of dye lead dose, the activity of SOD in cortex, cerebellum and hippocampus showed a downward trend, while the contents of H2O2 and MDA showed a rising trend. The activity of SOD was positively correlated with APE1 protein level in cortex, cerebellum and hippocampus (r=0.619, 0.380 and 0.375,P<0.05). While the contents of H2O2 and MDA were neg-atively correlated with APE1 protein level in cortex, cerebellum and hippocampus (r=-0.472,-0.535,-0.436,-0.514,-0.486 and-0.316,P < 0.05). Conclusion Lead exposure through drinking water can affect the expression of APE1 protein through inducing oxidative stress in brain tissues of rats.