锌、铁、维生素C对锰的细胞免疫毒性的拮抗作用观察
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摘要
目的 研究锌（Zn）、铁（Fe）、维生素C（VitC）对锰（Mn）
的细胞免疫毒性作用的影响。方法 利用体外培养的淋巴细胞，
采用正交试验设计，于染Mn的同时向培养液中补充Zn、Fe、VitC
三种营养素。用溴化四氮唑盐检测法（MTT法）测定T淋巴细
胞增殖功能和自然杀伤细胞（NK细胞）杀瘤细胞活性；用酶联
免疫吸附试验（ELISA）测定培养液中的白细胞介素-2（IL-2）
含量。结果 随着染Mn剂量的增大和染Mn时间的延长，T淋
巴细胞增殖功能、NK细胞杀瘤细胞活性及IL-2含量均显著下降。
在Zn、Fe、VitC对Mn的细胞免疫毒性的拮抗作用试验中，起
主要作用的是Zn，表现在随着培养液中Zn浓度增大和Fe/Zn=0
时，IL-2含量显著增大，NK细胞活性亦有随Zn浓度增大和干
预时间延长而升高的趋势。结论 适宜浓度的Zn对Mn的细胞
免疫毒性有拮抗作用。
Effects of Zinc,lron and L-ascorbic Acid on Antagonism to
cen -mediated Immunotoxicity Exposcd to Manganesc
School or Pubnc Htw Xinhag Mwhtal bohayyrumcto
Postgraduate Liu Fengjuan
Tutors Huang Xianyi Yao Haiytng
Abstract
l
Objective The effects of zinc,iron and L-ascorbic acid on cellmediated inmiunc~toxicity after exposure to manganese were slxidied.Methods Lymphocytes from peripheral blood mononuclear were cultured in RPMI1 640 basal medium with supplementation of zinc,iron and L-ascorbic acid when exposed to manganese. Lymphocyte proliferation and natural killer cell activity were assessed by meanes of MTT assay,and the concentration of IL-2 by ELISA.And orthogonal design were used to analyse data.Results Lymphocyte proliferation,NK activity and the concentration of IL-2 decreased when the concentration and the duration of exposure to manganese increased. Zinc was the most important factor in the antagonism of them to cellmediated immunotoxicity exposed to manganese. The concentration of IL-2 greatly increased when the concentration of zinc went up, and Fe/Zn=0.In addition,there was a tendency that NK activity went up as the concentration of zinc and antagonistic duration increased.Conclusi~n Appropriate concentration of z
inc could antagonize cell-mediated immunotoxicity induced by manganese.
的细胞免疫毒性作用的影响。方法 利用体外培养的淋巴细胞，
采用正交试验设计，于染Mn的同时向培养液中补充Zn、Fe、VitC
三种营养素。用溴化四氮唑盐检测法（MTT法）测定T淋巴细
胞增殖功能和自然杀伤细胞（NK细胞）杀瘤细胞活性；用酶联
免疫吸附试验（ELISA）测定培养液中的白细胞介素-2（IL-2）
含量。结果 随着染Mn剂量的增大和染Mn时间的延长，T淋
巴细胞增殖功能、NK细胞杀瘤细胞活性及IL-2含量均显著下降。
在Zn、Fe、VitC对Mn的细胞免疫毒性的拮抗作用试验中，起
主要作用的是Zn，表现在随着培养液中Zn浓度增大和Fe/Zn=0
时，IL-2含量显著增大，NK细胞活性亦有随Zn浓度增大和干
预时间延长而升高的趋势。结论 适宜浓度的Zn对Mn的细胞
免疫毒性有拮抗作用。
Effects of Zinc,lron and L-ascorbic Acid on Antagonism to
cen -mediated Immunotoxicity Exposcd to Manganesc
School or Pubnc Htw Xinhag Mwhtal bohayyrumcto
Postgraduate Liu Fengjuan
Tutors Huang Xianyi Yao Haiytng
Abstract
l
Objective The effects of zinc,iron and L-ascorbic acid on cellmediated inmiunc~toxicity after exposure to manganese were slxidied.Methods Lymphocytes from peripheral blood mononuclear were cultured in RPMI1 640 basal medium with supplementation of zinc,iron and L-ascorbic acid when exposed to manganese. Lymphocyte proliferation and natural killer cell activity were assessed by meanes of MTT assay,and the concentration of IL-2 by ELISA.And orthogonal design were used to analyse data.Results Lymphocyte proliferation,NK activity and the concentration of IL-2 decreased when the concentration and the duration of exposure to manganese increased. Zinc was the most important factor in the antagonism of them to cellmediated immunotoxicity exposed to manganese. The concentration of IL-2 greatly increased when the concentration of zinc went up, and Fe/Zn=0.In addition,there was a tendency that NK activity went up as the concentration of zinc and antagonistic duration increased.Conclusi~n Appropriate concentration of z
inc could antagonize cell-mediated immunotoxicity induced by manganese.
引文
1 Smialowicz RJ,Riddle MM,Rogers RR, et al. Enhancement of natural killer cell activity and interferon production by manganese in young mice. Immunopharmacol Immunotoxico,1988,10:93-107.
2 郭建霞，胡万达，纪淑琴，等．氯化锰对小鼠免疫毒性作用的研究．职业医学,1991，18：136-138．
3 Hallberg L,Rossander-Hulten L,Brune M,et al.Calcium and iron absorption:mechanism of action and nutritional importance.Eur J Clin Nutr, 1992,46: 317-27.
4 刘继文，赵效果．低锰作业对工人体内某些微量及常量元素的影响．中国工业医学杂志,1997,10：241-243．
5 魏美文，胡瑞梅，张岩．铁缺乏对鼠肝脏及脑组织7种微量元素的影响．微量元素与健康研究,1998,15：10-11．
6 Khandelwal S,Ashguin M, Tandon SK.Influence of essential elements on manganese intoxication. Bull Environ Contain Toxicol,1984,32:10-19.
7 刘起展，董国宾，赵跃，等．刺梨利康饮排锰效果的实验研究．中国公共卫生学报,1998,17：108-110．
8 Driessen C;Hirv k, Rink L,et al. Induction of cytokines by zinc ions in human peripheral blood mononuclear cellls and separated monocytes. Lymphokine Cytokine Res, 1994,13:15-20.
9 吴骏，任建梅，王素华，等．免疫功能检查在锰中毒普查中的作用初探．中华劳动卫生职业病杂志,1996,14：34-35．
10 周延冲．受体信号传导机理(二)．国外医学分子生物学分册,1998,10：19．
11 Chao SH,Suzuki Y,Zysk JR,et al.Activation of calmodulin by various metal cations as a function of ionic radius.Mol Pharmacol, 1984,26:75-82.
12 农清清，胡万达，谢佩意，等．锰对大鼠脑钙调素、Ca~(2+)-Mg~(2+)-ATP酶的影响及对氨基水杨酸钠的干预作用．中华劳动卫生职业病杂志,1997,15：365-366．
13 郑玉新．锰的神经毒性研究进展．国外医学卫生学分册,1997,24：129-132．
14 Sharma PK,Kaji E.Role of cyclic AMP in lymphocytes.Biochem Cell Biol, 1986,64:1072-1078.
15 万志红，杨家驹，靡漫天．锌对体外培养淋巴细胞功能的影响研究．上海免疫学杂志，1997，17：220-222．
16 Anastassion ED,Paliogianni F,Balow JP,et al.Prostaglandin E_2 and other cyclic AMP-elevating agents modulate IL-2 and IL-2R α gene expression at multiple levels. J Immunol, 1992,148:2845-2852.
17 Isakov N, Scholz W,Altman A. Signal transduction and intracelluar events in T-lymphocyte activation.Immunol Today, 1986,7:271-278.
18 Miller GG,Strittmatter WJ.Identification of human T cells that require zinc for growth. Scand J Immunol, 1992,36:269-77.
19 吴嘉惠，贺泽华，徐迪雄．缺锌对大鼠胸腺发育影响及机理探讨．营养学报，1998，20：303-307．
20 吴嘉惠，吴水冰，李才安．锌对免疫细胞的细胞周期影响的研究．中国免疫学杂志，1994，10：278-281．
21 Waring P,Egan M,Braithwaite A, et al. Apoptosis induced in macrophages and T blasts by the myotoxin sporidesmin and protection by Zn salts.Int J Immunopharmac, 1990,12:445-462.
22 余勤，詹起荪，吴康健．锌对营养不良小鼠脾脏NK细胞活性的影响．微量元素与健康研究，1998，15：15-16．
23 Salas M,kirchned H.Inducfion of interferon-γ in human leukocyte cultures stimulated by Zn~(2+).Clin Immunol Immunopathol, 1987;45:139-142.
24 Mckay RH,Higuchi DA,Winder WW, et al.Tissue effects of iron deficiency in the rat. Biochem Biophys Acta, 1983,757:352-358.
25 Kunibidila SR, Nauss KM,Balig SB,et al. Impairment of blastogenic response of splenic lymphocytes from iron-deficient mice.In vitro repletion by hemin, transferrin, and ferric-chloride,Am J Clin-Nutr,1983;37:557-565.
26 Park CH,kimler BF. Growth modulation of human leukemic,preleukemic,and myeloma progenitor cells by L-ascorbic acid.Am J Clin Nutr, 1991,54(6 suppl): 1241S-1246S.
27 Pierson BA,McGlave PB,Hu WS,et al.Natural killer cell proliferation is dependent on human serum and markedly increased utilizing an enriched supplemented basal medium. J Hematother, 1995,4:149-58.
2 郭建霞，胡万达，纪淑琴，等．氯化锰对小鼠免疫毒性作用的研究．职业医学,1991，18：136-138．
3 Hallberg L,Rossander-Hulten L,Brune M,et al.Calcium and iron absorption:mechanism of action and nutritional importance.Eur J Clin Nutr, 1992,46: 317-27.
4 刘继文，赵效果．低锰作业对工人体内某些微量及常量元素的影响．中国工业医学杂志,1997,10：241-243．
5 魏美文，胡瑞梅，张岩．铁缺乏对鼠肝脏及脑组织7种微量元素的影响．微量元素与健康研究,1998,15：10-11．
6 Khandelwal S,Ashguin M, Tandon SK.Influence of essential elements on manganese intoxication. Bull Environ Contain Toxicol,1984,32:10-19.
7 刘起展，董国宾，赵跃，等．刺梨利康饮排锰效果的实验研究．中国公共卫生学报,1998,17：108-110．
8 Driessen C;Hirv k, Rink L,et al. Induction of cytokines by zinc ions in human peripheral blood mononuclear cellls and separated monocytes. Lymphokine Cytokine Res, 1994,13:15-20.
9 吴骏，任建梅，王素华，等．免疫功能检查在锰中毒普查中的作用初探．中华劳动卫生职业病杂志,1996,14：34-35．
10 周延冲．受体信号传导机理(二)．国外医学分子生物学分册,1998,10：19．
11 Chao SH,Suzuki Y,Zysk JR,et al.Activation of calmodulin by various metal cations as a function of ionic radius.Mol Pharmacol, 1984,26:75-82.
12 农清清，胡万达，谢佩意，等．锰对大鼠脑钙调素、Ca~(2+)-Mg~(2+)-ATP酶的影响及对氨基水杨酸钠的干预作用．中华劳动卫生职业病杂志,1997,15：365-366．
13 郑玉新．锰的神经毒性研究进展．国外医学卫生学分册,1997,24：129-132．
14 Sharma PK,Kaji E.Role of cyclic AMP in lymphocytes.Biochem Cell Biol, 1986,64:1072-1078.
15 万志红，杨家驹，靡漫天．锌对体外培养淋巴细胞功能的影响研究．上海免疫学杂志，1997，17：220-222．
16 Anastassion ED,Paliogianni F,Balow JP,et al.Prostaglandin E_2 and other cyclic AMP-elevating agents modulate IL-2 and IL-2R α gene expression at multiple levels. J Immunol, 1992,148:2845-2852.
17 Isakov N, Scholz W,Altman A. Signal transduction and intracelluar events in T-lymphocyte activation.Immunol Today, 1986,7:271-278.
18 Miller GG,Strittmatter WJ.Identification of human T cells that require zinc for growth. Scand J Immunol, 1992,36:269-77.
19 吴嘉惠，贺泽华，徐迪雄．缺锌对大鼠胸腺发育影响及机理探讨．营养学报，1998，20：303-307．
20 吴嘉惠，吴水冰，李才安．锌对免疫细胞的细胞周期影响的研究．中国免疫学杂志，1994，10：278-281．
21 Waring P,Egan M,Braithwaite A, et al. Apoptosis induced in macrophages and T blasts by the myotoxin sporidesmin and protection by Zn salts.Int J Immunopharmac, 1990,12:445-462.
22 余勤，詹起荪，吴康健．锌对营养不良小鼠脾脏NK细胞活性的影响．微量元素与健康研究，1998，15：15-16．
23 Salas M,kirchned H.Inducfion of interferon-γ in human leukocyte cultures stimulated by Zn~(2+).Clin Immunol Immunopathol, 1987;45:139-142.
24 Mckay RH,Higuchi DA,Winder WW, et al.Tissue effects of iron deficiency in the rat. Biochem Biophys Acta, 1983,757:352-358.
25 Kunibidila SR, Nauss KM,Balig SB,et al. Impairment of blastogenic response of splenic lymphocytes from iron-deficient mice.In vitro repletion by hemin, transferrin, and ferric-chloride,Am J Clin-Nutr,1983;37:557-565.
26 Park CH,kimler BF. Growth modulation of human leukemic,preleukemic,and myeloma progenitor cells by L-ascorbic acid.Am J Clin Nutr, 1991,54(6 suppl): 1241S-1246S.
27 Pierson BA,McGlave PB,Hu WS,et al.Natural killer cell proliferation is dependent on human serum and markedly increased utilizing an enriched supplemented basal medium. J Hematother, 1995,4:149-58.