褪黑素对锰致小鼠运动障碍及纹状体损伤的影响  

Effects of melatonin on manganese-induced dyskinesia and striatum injury in mice

作　　者：邓宇[1] 米超[2] 李乐慧[1] 徐冬辉[3] 徐斌[1] 刘巍[1] 

机构地区：[1]中国医科大学公共卫生学院环境卫生学教研室,辽宁沈阳110001 [2]沈阳市卫生监督所学校卫生监督科,辽宁沈阳110024 [3]中国医科大学附属第一医院临床药理教研室,辽宁沈阳110001

出　　处：《中国工业医学杂志》2013年第6期403-405,408,F0003,共5页Chinese Journal of Industrial Medicine

基　　金：国家自然科学基金资助项目(编号81302406);教育部高等学校博士学科点专项科研基金联合资助课题新教师类(项目编号20112104120017)

摘　　要：目的探讨褪黑素对锰致小鼠运动障碍及纹状体损伤的影响。方法小鼠84只，均分为6组，分别为对照组及低、中、高Mn组，褪黑素（MT）对照组和MT＋高Mn组。第5、6组提前皮下注射给予5mg／kgMT，2h后，第2-4和6组分别腹腔注射给予12．5、25、50和50mg／kgMnCl2，连续2周。观察小鼠的自主活动情况，检测纹状体GSH-Px、SOD和γ-GCS的活力、表达及蛋白水平。结果随着锰浓度的升高，自主活动和站立次数逐渐减少；纹状体γ-GCS、GSH-Px和SOD活力、蛋白表达水平逐渐下降，并呈剂量-效应关系。与高锰组比较，MT干预组自主运动和站立次数增加明显（P〈0．05，P〈0．01）；γ-GCS、GSH-Px和SOD活力、阳性表达及蛋白水平均显著升高。结论本实验结果提示过量锰暴露可导致运动障碍及纹状体氧化损伤，褪黑素可能通过激活抗氧化酶GSH-Px、SOD和γ-GCS发挥对它的拮抗作用。Objective Study the effect of melatonin on manganese （Mn） -induced dyskinesia and striatum injury of mice. Methods Eighty-four mice were randomly divided into six groups： they were the control group, low-dose Mn group, mediumdose Mn group, high-dose Mn group, MT control group, and MT ＋ high Mn group. The mice in fifth and sixth groups were injected s. c with 5 mg/kg MT in advance, two hours later, all the mice except control and MT groups were injected i. p with 12. 5, 25, 50, and 50 mg/kg MnCl2, respectively everyday for two weeks. Observe the activity status of mice and detect the activity and expression levels of GSH-Px, SOD and γ-GCS in striatum. Results With the elevation of Mn exposure level, the frequency of activity and stand reduced, while the activity and expression of γ-GCS, GSH-Px and SOD in striatum were rised in a dose-dependent manner. Comparing with high-dose Mn group, autonomic activity and stand of mice in MT intervention group were increased significantly （P 〈 0. 05, P 〈 0. 01, respectively）, the activities and expression level of γ-GCS, GSH-Px, and SOD were also elevated obviously. Conclusion The results suggested that the excessive exposure of Mn might induce dyskinesia and oxidative damage of striatum, while melatonin could antagonize the effect by activating the antioxidant enzymes such as GSH- Px, SOD, and γ-GCS.

关 键 词：锰(Mn) 褪黑素(MT) 纹状体 运动障碍 氧化损伤 

分 类 号：R994.6[医药卫生—毒理学]