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甲醛对小鼠不同脑区的神经毒性作用

曹凤华, 蔡洁, 刘志敏, 李慧, 尤会会, 梅宇飞, 杨旭, 丁书茂

华中师范大学生命科学学院遗传调控与整合生物学湖北省重点实验室，武汉 430079

摘要

本研究旨在探讨甲醛导致机体神经系统病变的具体机制。选用雄性Balb/c小鼠为研究对象，动态吸入甲醛方式染毒7天，每天8 h，甲醛浓度分别为0、0.5、3.0 mg/m3，同时设置一氧化氮合酶(nitric oxide synthase, NOS)拮抗剂(NG-monomethyl- L-arginine, L-NMMA)组，该组小鼠同时进行3.0 mg/m3甲醛染毒。染毒结束后，用试剂盒检测小鼠大脑皮层、海马和脑干中环磷酸腺苷(cyclic adenosine monophosphate, cAMP)、环磷酸鸟苷(cyclic guanine monophosphate, cGMP)、一氧化氮(nitric oxide, NO)含量和NOS活性的变化。结果显示，与对照组相比，小鼠大脑皮层和脑干中cAMP含量在0.5 mg/m3染毒组显著升高(均P < 0.05)，但是在3.0 mg/m3染毒组显著降低(P < 0.05)，海马中cAMP含量仅在3.0 mg/m3染毒组出现显著降低(P < 0.05)；与对照组相比，L-NMMA拮抗组小鼠cGMP和NO含量分别在海马和大脑皮层中显著上升(均P < 0.01)，而cAMP含量和NOS活性在不同脑区中无显著变化。与3.0 mg/m3染毒组相比，L-NMMA拮抗组不同脑区中cAMP含量均显著上升(均P < 0.05)，NOS活性显著下降(P < 0.05或P < 0.01)；大脑皮层和脑干中的cGMP含量以及脑干中的NO含量亦出现显著性变化(P < 0.05或P < 0.01)。以上结果提示，甲醛暴露的神经系统毒性作用与NO/cGMP信号转导通路和cAMP信号通路存在一定的关系。

关键词： 甲醛; 小鼠; cAMP; NO/cGMP; 神经毒性

分类号：R3

[Toxic effect of formaldehyde on mouse different brain regions.] [Article in Chinese]

CAO Feng-Hua, CAI Jie, LIU Zhi-Min, LI Hui, YOU Hui-Hui, MEI Yu-Fei, YANG Xu, DING Shu-Mao

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Huazhong Normal University, Wuhan 430079, China

Abstract

The aim of this study was to explore the mechanism of the nervous system lesions induced by formaldehyde (FA). Male Balb/c mice were exposed to gaseous formaldehyde for 7 days (8 h/d) with three different concentrations (0, 0.5 and 3.0 mg/m3). A group of animals injected with the nitric oxide synthase inhibitor L-NMMA (0.01 mL/g) was also set and exposed to 3.0 mg/m3 FA. The concentrations of cAMP, cGMP, NO and the activity of NOS in cerebral cortex, hippocampus and brain stem were determined by corresponding assay kits. The results showed that, compared with the control (0 mg/m3 FA) group, the cAMP contents in cerebral cortex and brain stem were significantly increased in 0.5 mg/m3 FA group (P < 0.05), but decreased in 3.0 mg/m3 FA group (P < 0.05); The concentration of cAMP in hippocampus was significantly decreased in 3.0 mg/m3 FA group (P < 0.05). In comparison with the control group, L-NMMA group showed unchanged cAMP contents and NOS activities in different brain regions, but showed increased cGMP contents in hippocampus and NO contents in cerebral cortex (P < 0.05). In addition, compared with 3.0 mg/m3 FA group, L-NMMA group showed increased contents of cAMP and reduced NOS activities in different brain regions, as well as significantly decreased cGMP contents in cerebral cortex and brain stem and NO content in brain stem. These results suggest that the toxicity of FA on mouse nervous system is related to NO/cGMP and cAMP signaling pathways.

Key words: formaldehyde; mouse; cAMP; NO/cGMP; neurotoxicity

收稿日期：2015-04-16　　录用日期：2015-06-16

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引用本文：

曹凤华, 蔡洁, 刘志敏, 李慧, 尤会会, 梅宇飞, 杨旭, 丁书茂. 甲醛对小鼠不同脑区的神经毒性作用[J]. 生理学报 2015; 67 (5): 497-504.

CAO Feng-Hua, CAI Jie, LIU Zhi-Min, LI Hui, YOU Hui-Hui, MEI Yu-Fei, YANG Xu, DING Shu-Mao. [Toxic effect of formaldehyde on mouse different brain regions.] [Article in Chinese]. Acta Physiol Sin 2015; 67 (5): 497-504 (in Chinese with English abstract).