氯化甲基汞对大鼠脑神经细胞c-fos表达的影响  

Effect of methylmercury chloride on the c-fos expression in brain nerve cells of the rats

作　　者：郭丽[1] 毕晓颖[1] 张兴国 张彤[1] 凌翎[1] 王晓丽[2] 李志超[1] 

机构地区：[1]吉林省长春市吉林大学预防医学院毒理学教研室,130021 [2]长春市疾病预防与控制中心办公室

出　　处：《中华预防医学杂志》2001年第5期309-311,F003,共4页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金资助 ( 39770 6 5 5 )

摘　　要：目的　通过体内与体外实验相结合的方法研究氯化甲基汞 (MMC)对脑神经细胞c fos表达的影响 ,探讨甲基汞所致脑发育损伤的机制。方法　体外实验中 ,应用免疫细胞化学方法观察MMC对培养神经元c fos表达的影响。体内实验中 ,Wistar妊娠大鼠于妊娠 7～ 10d连续灌胃 ,每日给予MMC 4mg kg。取出生后第 1、3、5、7、10和 15d仔鼠大脑组织制备常规组织切片。采用免疫组织化学方法检测c fos表达。结果　体外培养的神经元中加入 0 3μmol LMMC持续作用后 ,神经元中c Fos阳性细胞率在 0 5h开始增多 ,并随时间的延长而增加。培养神经元接触MMC 10min和 2、6h组 ,细胞阳性率分别为 (6 97± 2 86 ) %、(6 6 86± 5 32 ) %、(6 4 49± 3 0 9) %。体内实验中 ,对照组和实验组中仔鼠大脑皮层中c Fos蛋白阳性细胞率随发育时间延长逐渐减少 ,但实验组均高于相应对照组 ,实验组第 1、3天组c Fos阳性率分别为 (4 7 0 1± 3 79) %和 (4 6 71± 1 96 ) % ,与对照组的 (35 86±3 0 4) %和 (33 35± 1 0 6 ) %相比 ,差异有非常显著性。结论　MMC可诱导脑神经细胞c fos的过表达 ,这可能是MMC所致脑发育损伤的机制之一。Objective In order to study the mechanism of injury in the brain development caused by methylmercury chloride (MMC) and its effects on the c-fos expression in brain nerve cells of the rats with experiments in vitro and in vivo. Methods In vitro, the effect of MMC on c-fos expression in the cultured nerve cells was observed by immunocytochemistry(SP method). In vivo, Wistar pregnant rats were administered 4 mg MMC per kg of body weight by a gastric tube from the 7 th to the 10 th gestational days. On the 1st, 3 rd, 5 th, 7 th, 10 th and 15 th days after birth, the rats were killed and tissue sections were prepared from their brain, respectively. The expression of c-fos was detected by SP method. Results The percentage of c-Fos-positive neuron in rat brain began to increase at 0.5 hours after being cultured in vitro with 0.3 μmol/L MMC continuously, and increased gradually as length of the exposure to MMC prolonged. The percentages of c-Fos-positive of cultured nerve cells in vitro were (6.97±2.86) %, (66.86±5.32) % and (64.49±3.09) % in the experimental groups exposed to MMC for 10 min, 2 h and 6 h, respectively. In vivo, the percentage of Fos-positive neuron nuclei decreased with development of neonatal rats. The percentage of c-Fos-positive neuron in the experimental groups was higher than that in the control groups and decreased with length of development. The percentages of c-Fos-positive neuron were (47.01±3.79)% and (46.71±1.96)% in the experimental groups 1 and 3 d,and (35.86±3.04)% and (33.35±1.06)% in the control group, respectively, with very significant difference. Conclusions It is concluded that MMC could induce c-fos over-expression in the nerve cells of the rat brain, which could explain the mechanism of injury to brain development caused by MMC.

关 键 词：氯化甲基汞化合物 神经元 脑发育损伤 C-FOS基因 大鼠 

分 类 号：R99[医药卫生—毒理学]