铅对四乙基铵诱导海马细胞外信号调节激酶2活力变化的影响  

The effect of lead exposure on active extracellar signal regulated kinase 2 induced by tetraethylammonium

作　　者：杨菁[1] 孙黎光[1] 宗志宏[1] 侯伟健[1] 

机构地区：[1]中国医科大学生物化学及分子生物学教研室,辽宁沈阳110001

出　　处：《毒理学杂志》2007年第1期16-19,共4页Journal of Toxicology

基　　金：国家自然科学基金(39970651)

摘　　要：目的探讨急、慢性铅暴露对四乙基铵(tetraethylammonium,TEA)诱导海马CA1区细胞外信号调节激酶2(extracellular signal-regulated kinase,ERK2)活力的影响。方法大鼠怀孕后开始饮用质量浓度为0.2%醋酸铅溶液,断乳后乳鼠则直接饮用,于30 d时,取幼鼠海马脑片稳定培养2 h,作为慢性染铅脑片;另取正常30 d幼鼠海马片稳定培养2 h后,为正常脑片。用TEA和或铅灌流脑片,并用不同的电压依赖型离子通道抑制剂进行处理,于不同时间收集脑片CA1区。用磷酸化抗体,以Western blots方法测定脑片ERK2活力。结果正常脑片组在TEA被冲洗掉10 min后ERK2活力比对照组升高了1.58倍,而22、5 min没有明显变化;nifedipine,L-VDCC抑制剂,可抑制ERK2活力升高。而TEA不能诱导预先用0.8,4.0,20.0μmol/L醋酸铅急性灌流脑片及慢性染铅脑片ERK2活力升高。结论染铅导致的学习记忆损害可能与其抑制活化ERK2含量升高有关,并且铅可能是通过阻止L-VDCC Ca2+内流来对TEA诱导活化ERK2含量升高产生抑制作用。Objective To investigate the effect of lead exposure on CA1 active Extracellar signal regulated kinase 2（ERK2） of rat hippocampus tatraethylammonium（TEA）. Methods For chronic lead exposure in vivo, pregnant female rats were given 0.2 % lead acetate in their drinking water before breeding and throughout gestation and lactation. After weaning at postnatal 21 d, the pups were provided lead acetate in drinking water. Until 30 d, hippocampus was got as chronic exposure sample. For acute lead expose in vitro, the control postnatal 30 d rat brains were got. After 2 h stabilization, lead acetate or （and） TEA was added into the ACSF, the slice was collected at different time and CA1 was got.The active ERK2 was determined by western blots. Results TEA increased active ERK2 10 min to 158% after the washout of TEA（ P 〈 0.01 ） and no significant increase in active ERK2 either 2 or 25 min. lead acetate could inhibit increase of active ERK2 induced by TEA. Nifedipine, L-type voltage dependent Ca^2＋ Channels（L-VDCC） antagonist, prevented the increase of active ERK2 measured at 10 min. Conclusion lead exposure inhibits increase of ERK2 activity, which may be the reason of its inhibition of LTP and learning and memory.

关 键 词：铅 海马 细胞外信号调节激酶2 L-电压依赖型离子通道 

分 类 号：R995[医药卫生—毒理学]