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应激的连续暴露和低剂量毒死蜱经皮给药对成年小鼠海马胶质纤维酸性蛋白表达的影响。

The effect of consequent exposure of stress and dermal application of low doses of chlorpyrifos on the expression of glial fibrillary acidic protein in the hippocampus of adult mice.

机构信息

Postgraduate & Research Department, International Medical University, No.126, Jalan 19/155B, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.

Pathology Department, International Medical University, No.126, Jalan 19/155B, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.

出版信息

J Occup Med Toxicol. 2011 Mar 8;6(1):4. doi: 10.1186/1745-6673-6-4.

DOI:10.1186/1745-6673-6-4
PMID:21385392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3061961/
Abstract

BACKGROUND

Chlorpyrifos (CPF), a commonly used pesticide worldwide, has been reported to produce neurobehavioural changes. Dermal exposure to CPF is common in industries and agriculture. This study estimates changes in glial fibrillary acidic protein (GFAP) expression in hippocampal regions and correlates with histomorphometry of neurons and serum cholinesterase levels following dermal exposure to low doses of CPF with or without swim stress.

METHODS

Male albino mice were separated into control, stress control and four treatment groups (n = 6). CPF was applied dermally over the tails under occlusive bandage (6 hours/day) at doses of 1/10th (CPF 0.1) and 1/5th dermal LD50 (CPF 0.2) for seven days. Consequent treatment of swim stress followed by CPF was also applied. Serum cholinesterase levels were estimated using spectroflurometric methods. Paraffin sections of the left hippocampal regions were stained with 0.2% thionin followed by the counting of neuronal density. Right hippocampal sections were treated with Dako Envision GFAP antibodies.

RESULTS

CPF application in 1/10th LD50 did not produce significant changes in serum cholinesterase levels and neuronal density, but increased GFAP expression significantly (p < 0.001). Swim stress with CPF 0.1 group did not show increase in astrocytic density compared to CPF 0.1 alone but decreased neuronal density.

CONCLUSIONS

Findings suggest GFAP expression is upregulated with dermal exposure to low dose of CPF. Stress combined with sub-toxic dermal CPF exposure can produce neurotoxicity.

摘要

背景

毒死蜱(CPF)是一种在全球范围内广泛使用的农药,已被报道会产生神经行为改变。皮肤接触 CPF 在工业和农业中很常见。本研究估计在皮肤暴露于低剂量 CPF 后,GFAP(胶质纤维酸性蛋白)在海马区的表达变化,并与神经元的组织形态计量学和血清胆碱酯酶水平相关,同时还研究了有无游泳应激的情况下。

方法

雄性白化小鼠分为对照组、应激对照组和四个处理组(n = 6)。CPF 通过封闭绷带在尾巴上进行皮肤涂抹(每天 6 小时),剂量为 1/10(CPF 0.1)和 1/5 皮肤 LD50(CPF 0.2),持续七天。随后还进行了游泳应激加 CPF 的处理。使用分光荧光法估计血清胆碱酯酶水平。用 0.2%硫堇对左海马区的石蜡切片进行染色,然后计数神经元密度。用 Dako Envision GFAP 抗体处理右海马切片。

结果

CPF 在 1/10 LD50 的应用并未导致血清胆碱酯酶水平和神经元密度发生显著变化,但显著增加了 GFAP 表达(p < 0.001)。与单独使用 CPF 0.1 组相比,CPF 0.1 加游泳应激组的星形胶质细胞密度没有增加,但神经元密度降低。

结论

研究结果表明,皮肤接触低剂量 CPF 会导致 GFAP 表达上调。应激与亚毒性皮肤 CPF 暴露相结合会产生神经毒性。

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