PAS-Na对锰中毒大鼠学习记忆功能障碍及海马结构GFAP表达的影响
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:探讨PAS-Na对染锰大鼠学习记忆障碍及海马结构胶质原纤维酸性蛋白(GFAP)阳性细胞表达的影响。
     方法:雄性SD大鼠144只在1~12周时随机分为空白组36只、染锰组72只﹑PAS-Na预防组36只。染锰组腹腔注射(ip)氯化锰(MnCl2·4H2O 15mg/kg),空白组腹腔注射等容量生理盐水,每日1次,每周5天,连续12周。PAS-Na预防组在每周的1、3、5天染锰结束后再背部皮下注射(sc)PAS-Na 200mg/kg;在染锰12周结束后把染锰组再随机分为染锰对照组(染锰组),PAS-Na治疗组,PAS-Na治疗组给予背部皮下注射PAS-Na 200mg/kg,染锰组和空白组给予背部皮下注射等容量的生理盐水,每日1次,每周3天,共6周。采用Morris水迷宫检测大鼠学习记忆能力,免疫组织化学方法检测海马CA1区和齿状回GFAP阳性细胞数。
     结果:染锰末周大鼠体重增加趋势明显减低,PAS-Na治疗使染锰大鼠体重增加,差异有统计学意义(P<0.05)。在第18周染锰组逃避潜伏期比空白组延长,但(P﹥0.05),PAS-Na治疗组在实验的1、2天游泳总路程比染锰组缩短(P<0.05)。在第6周、12周及18周染锰组GFAP阳性细胞数比空白组多(P <0.05~0.01),在12周PAS-Na预防组GFAP阳性细胞数较染锰组减少(P<0.05),但仍较空白组多。
     结论:锰暴露使大鼠体重增加趋势减缓和学习记忆能力下降,海马胶质原纤维酸性蛋白(GFAP)表达增加,PAS-Na对锰致大鼠生长发育迟缓,学习记忆障碍和海马胶质细胞异常增生可能有干预作用。
Objective: To explore the effects of sodium para-aminosalicylic acid (PAS-Na) on learning memory and expression of glial fibrillary acidic protein (GFAP) positive cells in hippocampus of subacute manganese(Mn)-exposed rats.
     Methods:144 male Sprague-Dawley rats were randomly divided into the control, Mn-exposed, PAS-Na prevention group. The Mn-exposed rats received daily intraperitoneally injections (i.p.) of manganese chloride (MnCl2·4H2O 15mg/kg), one time a day , 5 days/week for 12 weeks, The control group were injected with the same Capacity saline。PAS-Na prevention group in the same time exposed to manganese 1,3,5 days a week subcutaneous injection (sc) PAS-Na 200mg/kg, Manganese in the dye after the end of 12 weeks of Mn group was randomly divided into control group exposed to manganese (Mn in group), PAS-Na treatment group,The treatment group after 12 weeks of Mn given subcutaneous injection of PAS-Na 200mg/kg, Exposed to manganese group and control group were given subcutaneous injection of the same volume of saline, 1 day, 3 days per week for 6 weeks.The ability of learning memory was tested by Morris Water Maze (MWM) and the GFAP-positive cells in the hippocampal CA1 area and dentate gyrus was detected by immunohis to chemical technique.
     Results:The weight gain of Mn-exposed group was evidently reduced in 12 weeks and still lasted 18 weeks after suspending Mn exposure (P<0.05). In the 18 week,The escape latency of Mn-exposed group were longer than those of the control group but(P﹥0.05), In the 1,2 days ,The total swimming distance of PAS-Na treatment group were shorter than those of the Mn-exposed group(P<0.05).In the 6 week、12 week and 18 week GFAP positive cells in the manganese-exposed group increased compared with that of control group(P <0.05~0.01),In the 12 week ,GFAP positive cells in the manganese-exposed group decreased compared with that of manganese-exposed group,But still more than the control group。
     Conclusions : PAS-Na may have the intervention effect on growth retardation,learning and memory impairment, glial abnormal proliferation in hippocampus of rats induced by manganese.
引文
1.贺新红,张德兴.锰接触对新生大鼠脑发育的时空影响因素研究[J].卫生研究,2005,2(34):161-162.
    2. Tomas - CamardielM, Herrera AJ, Venero JL, et al. Differential regulation of glutamic acid decarboxylase mRNA and tyrosine hydroxylase mRNA exp ression in the aged manganese - treated rats [J]. Brain ResMol Brain Res,2002,103 (12):116-129.
    3. Perl DP , Olanow CW. The Neuropathology of Manganese-Induced Parkinsonism[J]. Neuropathol Neurol,2007,66(8):675-682.
    4.许晓利,杨敏,向赟.亚急性外源性锰中毒对大鼠海马的影响郧[J].阳医学院学报,2007,26(3):144-146.
    5. Aschner M,Aschner JL. Mercury neurotoxicity : mechanism of blood-brain barrier transport [J] . Neurosci Biobehav Rev,1990 , 14 (1) : 169 - 176.
    6.Murphy VA, Rosenberg JM. Smith QR, et al . Elevation of brain manganese in calcium2deficient rats [J] . Neurotoxico2 logy,1991,12 (1) : 255 - 264.
    7.Gallez B, Baudelet C, Geurts M. Regional distribution of manganese found in the brain after injection of a single dose of manganese2based contrast agents [J] . Magn Reson Imagi ng.1998,16 (10): 1211 - 1215.
    8.谭国鹤,杨伯宁,谭国富,等.锰中毒对小鼠海马神经肝细胞殖的影响[J].中华劳动卫生职业病杂志,2007,25(5):282-285.
    9. Xu XL,Xiang Y,Yang M. Subacute toxicity of exogenous manganese on rat hippocampal neurons [J]. Neural Regeneration Research,2008,3(5): 550-553.
    10.徐斌,陈俊抛,林煜.去松果体对大鼠学习记忆及海马结构星形胶质细胞的影响[J].中国行为学科学,2000,9(3):188-192.
    11. Ky SQ,Deng HS,Xie PY,et al. A report of two cases of chronic serious manganese poisoning treated with para-aminosalicylic acid[J]. Br J Ind Med, 1992, 49(1): 66-69.
    12. Jiang YM,Mo XA,Du FQ,et al. Effective treatment of manganese-induced occupational parkinsonism with PAS-Na: A case of 17-year follow-up study[J]. J Occup Environ Med, 2006,48(6): 644-649.
    13.郭菲烨,区仕燕,姜岳明,等.对氨基水杨酸钠治疗一例锰中毒致书写过小征疗效的长期追踪观察[J].广西医科大学学报,2007,24(2):300-302.
    14.高晓玲,蒋志宏,刘卓宝,等.对氨基水杨酸钠与EDTA治疗慢性锰中毒疗效对比[J].劳动医学,2001,18(3):154-156.
    15.姜岳明,吕劲.锰中毒治疗的某些药物研究概况[J].职业医学,1993 ,20 (5) :303-304.
    16.洪息君,黄志明,陈家欢.等.锰在染毒大鼠体内的分布及对氨基水杨酸钠对锰体内分布的影响[J].广西医学,1991,13(1):23-24.
    17. Ky Shuqin,Deng Haishang,Xie Peiyi,et al . A report of two cases of chronic serious manganese poisoning treated with sodium para-aminosali- cylic acid[J]. BrJInd Med,1992,49 (1):66-68.
    18. Zheng W,Jiang YM,Zhang Y,et al. Chelation therapy of manganese intoxication with para-aminosalicylic acid (PAS) in Sprague-Dawley rats [J]. Neurotoxicol,2009,30(2):240-248.
    19.邓祥发,陈海滨,姜岳明,等. PAS-Na对亚急性锰暴露大鼠学习记忆及海马超微结构的影响[J].毒理学杂志,2010,24(1): 5-9.
    20.张忠诚,张忠玺,张荣广.锰与人体健康[J].微量元素与健康研究,2003,20(2):59-60.
    21.宋世震,彭晓武,范丽蓉.孕期锰染毒对仔鼠脑、肝AchE的影响[J].武汉科技大学学报,2004,27(1):84-85.
    22.张本廷,朱长才,叶方立,等.锰对大鼠子代神经行为发育的影响[J].中国职业医学,1999,26(6):5-7.
    23.宋世震,张本延,范丽蓉.孕期锰染毒对仔鼠脑、肝SDH活性的影响[J].中国冶金工业医学杂志,2004,21(2):87-88.
    24.付承红,邹云锋,王承敏,等.父母职业性接锰对其子女智力的影响[J] .中国职业医学,2004,31(2):26-28.
    25.吴卫平,孙瑜,蒋学之,等.锰在小鼠睾丸和脑分布及对氨基水杨酸钠驱锰实验的研究[J].中华劳动卫生职业病杂志,1993,11(3):143-146.
    26.鲁力,陆继培,农清清,等.对氨基水杨酸钠对染锰大鼠睾丸细胞内钙离子调节酶的影响[J] .中国职业医学,2000,27(2):16-18.
    27.黄世文,郭松超,陆彩玲.牛磺酸对染锰大鼠海马神经毒性的影响[J].中国职业医学,2008,35(5):374-377.
    28.姜岳明,葛利辉,陆继培,等.对氨基水杨酸钠对锰中毒大鼠体内锰、铜水平的影响[J].中国药理学与毒理学杂志,1992,6(3):185-188.
    29. Schneider JS,Decamp E,Koser AJO,et al. Effects of chronic manganese exposure on cognitive and motor functioning in non-human Primates[J]. Brain Research,2006,11(8): 222-231.
    30.秦景香,周敏,曹刚,等.集装箱制造业电焊工神经行为功能的调查分析[J].环境与职业医学,2005,22(4): 335-337.
    31.张文红,薛梅,郝静静,等.锰电焊作业工人神经行为功能的调查[J].工业卫生与职业病,2006,32(2): 98-100.
    32.陈骥光,姜欣明,林彬,等.锰接触—行为功能关系的研究[J] .工业卫生与职业病,1995,21 (4) : 200-202.
    33. Lucchini R,Selis L,Folli D,et al. Neurobehavioral effects of manganese in workers from a ferroalloy plant after temporary cessation of exposure [J] . Scand J work Environ Health,1995,21 (2) : 143-149.
    34.牛心华.锰作业女工生殖机能调查[J].河南预防医学杂志,2008,19(4):264-277.
    35. Saitoh Y,Kimura S,Nezu A,et al. Hyperintense brain lesionson T1-weighted MR after parenteral nutrtion [J ] . No To Hattatsu , 1996 , 28(1) : 39-43.
    36. Newland MC. Persistent effects of manganese on effortful responding and their relationship to manganese accumulation in the primate gland pallidus[J] . Toxicol Appl Pharmacol , 1992 , 113(6): 87-97.
    37.肖忠新,牛丕业,李慧,等.锰对大鼠空间学习记忆影响[J].中国公共卫生,2010,26(3):381-382.
    38.张德兴,贺新红,黄绍明,等.锰中毒对新生小鼠脑发育的影响[J].卫生研究,2001,30(5):260-262.
    39.温静,杨伯宁,任丹.枸杞多糖对锰中毒小鼠神经发生和学习记忆的影响[J].中国中西医结合杂志,2010,30(3):295-298.
    40.贺新红,张德兴,无燕明,等.生后锰接触对小鼠中脑被盖发育的毒性影响[J].解剖学研究,2005,27(1):7-9.
    41.李积胜,汪超,王静,等.锰对大鼠海马神经微丝蛋白表达的影响[J].武警医学院学报,2000,9(4):236-238.
    42.刘立国,王荔,郭碧凝,等.锰污染区儿童神经行为调查研究[J].中国预防医学杂志,2007,8(4):384-385.
    43. Hazell AS.Astrocytes and manganese neurotoxicity[J].Neurochem Int,2002,41(4):271-277.
    44.寇盛斌,吕来清,潘三强.大鼠在学习记忆时内侧隔核星形胶质细胞GFAP表达的变化[J].解剖学研究,2004,26(4):245-246.
    45.王培安,刘卓宝,赵金垣,等.职业病临床指南.上海医科大学出版社,1995. 302-306.
    46.李习艺,郭松超,唐深,等.锰对神经细胞超微结构的影响[J].卫生毒理学杂志, 2004,18(4):291-293.
    47. Mcmillan DE. A brief history of the neuro behavioral toxicity of manganese: some unanswered questions[J]. Neurotoxicology,1999,20(3): 499- 507.
    48.王悦,段春礼,张海燕,等.锰对多巴胺能神经元毒性的研究[J] .神经解剖学杂志,2001,17(1):57-61.
    49. Shen XM,Dryhurst G. Iron and manganese catalyzed autoxida2 tion of dopamine in the presence of L2cysteine :possible insights into iron and manganese mediated dopaminergic neurotoxicity. [J]. Chem Res Toxicol ,1998 ,11(2):824-837.
    50.贺新红,张德兴,陈伟强.大鼠生后锰接触对黑质多巴胺能神经元发育的毒性影响[J].卫生研究,2004,33(6):667-668.
    51. Desole MS,Seiola L,Delogu MR,etal.Manganese and Etrahy dropyridine induce apoptosisin PC12 cells[J].NeuroseiLett,1996,209(3):193-196.
    52.龙大宏,杨丹迪,李佳楣.穹窿海马伞损伤对成年鼠学习记忆和海马GFAP阳性细胞的影响[J] .广州医学院学报,2001,29(4):1-4.
    53.廖敏,陈世新.慢性捆绑应激致大鼠学习记忆受损及海马胶质细胞GFAP表达的变化[J].咸宁学院学报,2003,17(5):322-324.
    54. Landfield PW,Rose G,Sandles L,et al.Patterns of astroglial hypertrophy and neuronal degeneration in the hippocampus of aged memory-deficient rat[J].J Geroncol,1997,32(1):3-6.
    55. Vezér T,Kurunczi A,Náray M,et al. Behavioral effects of subchronic inorganic manganese exposure in rats [J].Am J Ind Med,2007,50 (11):841-852.
    56.姚应林.用对氨基水杨酸钠对锰中毒作诊断性治疗一例报告[J].卫生研究, 2000,2(34):161-162.
    57.吴萍.对氨基水杨酸钠诊断性治疗轻度锰中毒1例报告[J].工业卫生与职业病,1991,17(3):163.
    58.吴卫平,孙瑜,蒋学之,等. 54锰在小鼠睾丸和脑分布及对氨基水杨酸钠驱锰实验的研究[J].中华劳动卫生职业病杂志,1993,11(3):143-146.
    59.Asanuma M,Miyazaki I,Ogawa N. Neuroprotective effects of nonsteroidal anti-inflammatory drugs on neurodegenerative diseases [ J ] . Current Pharmaceutical Design,2004,10(3):695-700.
    60.高艳书.慢性职业锰中毒的护理[J] .昆明医学院学报,2007,11(2): 288-289.
    61.罗静.在职业病人护理中给予人文关怀[J].中国社区医师,2006,22(8):113.
    62.高天丽,孟福新,孙慾君.药源性亚急性铅中毒护理体会[J].中国职业医学,2001,2(28):18-19.
    63.徐月明.职业病患者的心理护理[J].职业医学,1997,24 (4):36.
    [1] Atsushi T. Manganese action in brain function [J]. Brain Research Review, 2003,(41): 79-87.
    [2]贺新红,张德兴.锰接触对新生大鼠脑发育的时空影响因素研究[J].卫生研究, 2005,2(34):161-162.
    [3] Greger JL. Dietary standards for manganese: over lap between nutritional and toxico logical studies[J]. Neurology,1998,12(8): 368-371.
    [4] Kalia K, Jiang W, Zheng W. Manganese accumulates primarily in nuclei of cultured brain cells[J]. Neurotoxicology,2008,29(3):466-470.
    [5]朱方争.锰的神经毒性及其早期生物学效应研究进展[J].医学文选, 2002, 5(21):33-35.
    [6] Tomas– Camardiel M, Herrera AJ , Venero JL, et al. Differential regulation of glutamic acid decarboxylase mRNA and tyrosine hydroxylase mRNA exp ression in the aged manganese - treated rats [J]. Brain Research Review,2002,103(12):116-129.
    [7]邓宇,冬辉,徐斌.氯化锰致大鼠神经毒性机制的研究[J].中国工业医学杂志,2008,2(21):21-22.
    [8]王守正,李鑫铭.长期接触锰对锥体束的影响[J].中国厂矿医学,2004,6(17):523-524.
    [9]高玉秋.锰对体内脂质过氧化及抗氧化酶的影响[J].铁道劳动安全卫生与环保, 2003, 4(30):199-200.
    [10] Lucchini R , Selis L , Folli D , et al . Neurobehavioral effects of manganese in workers from a ferroalloy plant after temporary cessation of exposure [J] . Scand work Environ Health,1995,21(2):143-149.
    [11] Mergler D, Huel G,Bowler H, et al.Nervous system dvs function amongworkers with long-term exprosure to manganese[J]. Environ RE, 1994, 64(2):151-160.
    [12] Racette BA, Mcgee-minnich L, Moerlein SM, el ta. Welding—related parkinsonism clinical features[J]. Treatment and pathophysiology, 2001, 56(1): 8-15.
    [13]吴萍,张杰,李洁.锰的神经毒性机制探讨[J].中国公共卫生, 2005, 7(21):800-802.
    [14] Wennberg A, Iregren A, Struwe G, et al. Manganese exposure in steel smelter a health hazard to the nervous system[J]. Scand work Environ Health, 1991, 17(6):255-262.
    [15] Huang CC,Chun S,Lu CS, et al. Ten Years of follow up Parkinson’s disease [J]. Neurology , 1998,50:69-81.
    [16] Olanow CW. Manganese-induced parkinsonism and Parkinson’s disease[J]. Ann N Y Acad Sci, 2004, 101(2):209-223.
    [17] Torrente M, Colomina MT, Domingo JL. Behavioral effects of adult rats concurrently exposed to high doses of oral manganese and restraint stress[J]. Toxicology, 2005, 211(1-2):59-69.
    [18] McKinney. Diffusion abnormalities of the globi pallidi in manganese neurotoxicity[J]. Neuroradiology, 2004, 4(46):291.
    [19] Kawamura W. Disgust-specific impairment of facial expression recognition in Parkinson's disease[J]. Brain, 2006, 3(129):707.
    [20] Dorman DC,Struve MF,James RA,et a1. influence of particles solubilityon the delivery of in haled manganese to the rat brain:manganese sulfate and manganese tetroxide pharmacokineties follow in grepeated(14days)exposure[J]. Toxieol Appl Pharmaeol, 2001, 70:78-87.
    [21]张德兴,贺新红,黄绍明,等.小鼠生后锰接触对脑发育的毒性影响[J].卫生研究,2002,31(7):73-75.
    [22]张先平,才秀莲.锰对大鼠生精细胞凋亡及p53和Bcl-2表达的影响[J].环境与健康杂志, 2007, 4(24):62-64.
    [23]吴松林,郭松超,秦绚.锰对大鼠纹状体神经细胞凋亡的影响[J].中华劳动卫生职业病杂志, 2007, 11(25):657-659.
    [24] Takeda A,Sotogaku N. Influe Bee of manganese on the release of neurotrans mitters in rat striatum [J]. Brain,2003,965(12):279-282.
    [25]王悦,段春礼,张海燕.等.锰对多巴胺能神经元毒性的研究[J].神经解剖学杂志, 2001, 17(1):5.
    [26] Shinotoh H,Snow BJ,Hewitt KA,et al. MRI and PET studies of manganese-intoxicated monkeys [J]. Neurology,1995,45:1199-1204.
    [27] Newland MC,Ceekler TL,Kordower JH,et al.Visualzing manganese in the Primate basal ganglia with magnetie resonanee imaging[J]. ExP Neurol,1989,106:2051-2058.
    [28] Olanow C . Manganese induced parkinsonism and Parkinson’s disease[J]. Ann N Y Acad Sci, 2004, 1012: 209-223.
    [29] Eriksonv KM,Tedroff J,Thuomas KA, et al. Manganese induced brain Lesions in Macaca fascicularis as revealed by Positron emission tomograPhy And magnetic resonance imaging[J]. Arch Toxicol, 1997, 66: 403-407.
    [30] Jankovic J. Searching for a relationship between manganese and welding and Parkinson’s disease[J]. Neurology, 2005, 64(12): 2021-2028.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700