醋酸铅饮水染毒对小鼠皮层神经元PKB/PI3Ks表达的影响  

Effect of chronic lead exposure on expression of PI3Ks/PKB pathway in cortical neuron of mice

作　　者：彭博[1] 游园园[2] 高双[2] 孙黎光[2] 

机构地区：[1]中国医科大学门诊部,辽宁沈阳110001 [2]中国医科大学生物化学与分子生物学教研室

出　　处：《毒理学杂志》2012年第2期91-94,共4页Journal of Toxicology

基　　金：国家自然科学基金资助项目(39970651)

摘　　要：目的观察铅暴露对小鼠大脑皮层神经元PI3Ks/PKB途径的影响。方法昆明系小鼠出生第一天通过饮水饲以不同浓度醋酸铅(1.2、2.4、4.8和9.6 mmol/L)6周,对照组饲以等量自来水,制备染铅模型。6周后用石墨炉原子吸收光谱法测血铅脑铅浓度;用Western blot法观察各组小鼠大脑皮层神经元PI3Ks、PKB总量(t-PKB)及磷酸化PKB(p-PKB)的表达状况。结果慢性染铅组小鼠大脑皮层神经元PI3Ks表达水平呈下降趋势,各染铅组PI3Ks表达与对照组比较,差异有统计学意义,并具有浓度效应关系(P<0.05)。PI3Ks表达与血铅浓度呈负相关(r=-0.82,P<0.01)。染铅组小鼠大脑皮层神经元p-PKB磷酸化均明显降低,并呈浓度依赖性。p-PKB磷酸化与血铅浓度呈负相关(r=-0.82,P=0.028),铅对小鼠大脑皮层神经元细胞t-PKB的磷酸化没有影响。结论铅暴露可使大脑皮层神经元细胞PI3Ks/PKB途径的表达水平下降。这可能是铅导致学习记忆功能损伤的原因之一。Objective To explore the Effect of PI3Ks/ PKB in cortical neuron of mice exposed to chronic lead.Methods Chronic acetic lead（1.2,2.4,4.8,9.6mmol/L） exposure was applied on KunMing mice for 6 weeks at postnatal.At the end of 6 weeks.the expression of PI3Ks,total PKB（t-PKB） and phosphorylated PKB（p-PKB） was determined by Western blots.Results Compared with control group the expression of PI3Ks in cortical neuron of lead group was decreased significance in a dose-dependent manner（P0.05）.The expression of PI3Ks in cortical neuron was negative correlation with concentration of blood lead,brain lead（r=-0.82,P0.01）.The expression of p-PKB in cortical neuron of lead group was decreased significance in a dose-dependent manner.The phosphorylation of p-PKB in cortical neuron was negative correlation with concentration of blood lead,brain lead（r=-0.82,P=0.028）.Total PKB protein levels did not change under the same experimental conditions.Conclusion The expression of PI3Ks and p-PKB decreased induced by lead in cortical neuron,which was maybe the one of the reasons of the damage of learning and memory induced by lead in mice.

关 键 词：铅 磷脂酰肌醇3激酶(PI3Ks) 蛋白激酶B(PKB) 大脑皮层神经元 

分 类 号：R995[医药卫生—毒理学]