铅对仔鼠海马蛋白激酶C和钙调蛋白基因表达与学习记忆的影响

Effects of lead exposure on protein kinase C and calmodulin expression in hippocampus and neurobehavioral function of baby rats

目的观察慢性铅染毒对仔鼠海马蛋白激酶C（PKC）、钙调蛋白（CaM）mRNA表达的影响，探讨铅神经毒性的分子机制。方法孕鼠随机分为对照组、0．2％醋酸铅染毒组和1．0％醋酸铅染毒组，从妊娠第0天开始通过自由饮水染毒。幼鼠出生后，先通过哺乳接触铅，断乳后则自行饮用与其母鼠相同的饮用水。出生后8d内行悬崖回避试验，50d行跳台试验，随后处死仔鼠，原子吸收光谱法测定脑铅含量，反转录-聚合酶链反应（RT-PCR）法观察各组仔鼠海马PKC、CaM的mRNA表达情况。结果同一发育时期的染铅组仔鼠脑铅含量明显高于对照组，差异有统计学意义（P〈0．01）；同一剂量染铅组出生后50d仔鼠脑铅含量明显高于生后8d，差异有统计学意义（P〈0．01）。染铅组仔鼠悬崖回避试验完成率和跳台学习成绩明显低于对照组，差异有统计学意义（P〈0．05，P〈0．01）。不同发育时期的1．0％醋酸铅染毒组仔鼠海马的PKC、CaM的mRNA表达下降（分别为0．53±0．04、0．59±0．02和0．65±0．01、0．62±0．01），与相应的对照组相比，差异有统计学意义（P〈0．05，P〈0．01）。结论慢性铅染毒可使仔鼠海马PKC、CaM的mRNA表达降低，这可能是铅致仔鼠学习记忆功能损害的分子机制之一。

Objective To observe the effect of chroric lead contaminant on mRNA expression of protein kinase C（ PKC ） and calmodulin（ CaM ） in hippocampus of baby rats. Methods The Wistar pregnant rats were randomly divided into 3 groups fed with distilled water and lead contained water（0.2% and 1.0% lead actate） respectively. The lead exposure period was from the 0 day of pregnancy to the day when the offspring weaned. Then the baby rats were fed with lead water the same as their mothers. The cliff avoidance reflex within postnatal day 8 and step down test at postnatal day 50 were performed. Then pups were killed at postnatal day 8 and 50 respectively. Atomic absorption spectrometry was used to determine lead content of rats＇ brain. RT-PCR was used to observe mRNA expression of PKC and CaM in hippocampus of baby rats. Results The brain lead content of test groups were much higher than that of the control group. The completion rate of cliff avoidance reflex and the score of step down test of test groups were lower than those in the control group （P〈 0.05 ）. Compared with control group, PKC and CaM mRNA expression of chronic lead exposure baby rats in the hippocampus had the downtrend （P〈0.05）. Conclusion The decrease of PKC and CaM mRNA expression level in hippocampus has a great link with the impairment of learning and memory induced by lead in baby rats, which might be one of the molecule mechanisms of lead induced impairment of learning and memory.