摘 要: 研究锰对小鼠纹状体多巴胺系统的影响以及褪黑素(MLT)的干预作用,为锰中毒机制的研究提供理论依据。方法 小鼠70只,随机均分为(1)对照组、(2)氯化锰组、(3)低MLT+氯化锰组、(4)中MLT+氯化锰组、(5)高MLT+氯化锰组。第1、2组皮下注射(sc)0.9%氯化钠,第3~5组sc给予1.25、2.5和5 mg/kg MLT;2h后,第1组腹腔注射(ip)0.9%生理盐水,第2~5组ip给予50 mg/kg MnCl2。每天1次,连续2周。ELISA检测黑质内多巴胺(DA)含量,免疫组织化学及western blotting检测DAT和DRD1的蛋白水平。 结果 与对照组相比,氯化锰组上述指标均出现了不同程度的降低,纹状体DA含量显著降低69,97%(P<0.01),免疫组织化学结果显示DAT和DRD1积分光密度分别下降62,54%和66,61%(P<0.01),DAT和DRD1的蛋白水平均明显降低;与氯化锰组相比,随着MLT浓度的升高,DA含量、DAT和DRD1表达量逐渐上升,并呈剂量 效应关系。 结论 过量锰暴露可导致纹状体多巴胺系统的损伤,褪黑素可以拮抗锰所致的上述变化 |
关键词: 锰 纹状体 多巴胺 多巴胺转运体 多巴胺受体 褪黑素 |
中图分类号: R994.3
文献标识码:
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基金项目: 国家自然科学基金项目(编号:81302406) |
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Effect of melatonin on Mn-induced dopaminergic system dysfunction in striatum of mice |
JIAO Cong cong,DENG Yu,XV Bin,SONG Qi fan,LIU Wei,XV Zhao fa
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Department of Environmental Health,School of Public Health,China Medical University,Shenyang 110122,China
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Abstract: Study the effect of Mn-induced dopaminergic system dysfunction in striatum of mice and the effect of melatonin(MLT)on it, thereby explore the pathogenesis of manganism. Methods Seventy mice were randomly divided into five groups:control group, Mn treated group,low MLT+Mn group,medium MLT+Mn group, and high MLT+Mn groups.The mice of different groups were subcutaneously injected with 0.9% NaCl,1.25 mg/kg、2.5 mg/kg and 5 mg/kg MLT respectively,two hours later,the control mice were ip given 0.9% NaCl,the mice in another four groups were ip injected with 50 mg/kg MnCl2.DA levels were determined by ELISA assay kits,expressions of dopamine transporter(DAT)anddopamine receptor 1(DRD1)were observed by immunohistochemistry method,protein levels of DAT and DRD1 were determined by western blotting. Result The results showed that DA levels in striatum of Mn treated mice was decreased 69.97%(P<0.01),the DAT and DRD1 were decreased by 62.54% and 66.61% in IOD(Integral optical density),respectively(P<0.01),while with the increase of MLT concentrations,the levels of DA,DAT,and DRD1 in striatum were all increased in a MLT concentration dependent manner. Conclusion It is suggested that Mn exposure may induce dysfuction of dopaminergic systems in striatum of mice,while MLT can antagonize the changes by Mn mentioned above. |
Keywords: manganese striatum dopamine dopamine transporter(DAT) dopamine receptors(DRT) melatonin(MLT) |