慢性碘过量对Wistar大鼠甲状腺抗氧化能力的影响
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摘要
目的
以基础是低碘摄入和正常碘摄入的两种碘营养状态的Wistar大鼠为研究对象，动态观察慢性轻中度碘过量对甲状腺氧化损伤和抗氧化能力的影响以及对甲状腺功能的影响，同时做尿碘监测，以保证所选用的碘浓度能符合试验目的的要求。
方法
1．实验动物分组和处理①低碘动物：4周龄Wistar大鼠160只饲以低碘饲料和双蒸水，三个月后复制出低碘甲肿模型，处死10只，剩余150只随机分为三组：低碘对照组、低碘Ⅰ组和低碘Ⅱ组。各组分别饲以双蒸水、含碘100μg／L和330μg／L的碘酸钾水。②普通动物：4周龄Wistar大鼠150只饲以普通饲料和双蒸水，三个月后随机分为三组：正常对照组、高碘Ⅰ组和高碘Ⅱ组。各组分别饲以双蒸水、含碘300μg／L和660μg／L的碘酸钾水。在给予处理因素的1、2、4、8、24周时分别处死大鼠，每次每组处死10只。
2．动物标本采集及制备①尿液：处死前一天将大鼠放入代谢笼中，自由进食及饮水，收集24小时尿液，-20℃冰箱中保存。②血浆：大鼠称体重，乙醚麻醉后，心脏采血，分离血浆，-20℃冰箱中保存。③甲状腺：大鼠经心脏采血处死后，迅速分离甲状腺，去除表面结缔组织，电子天平称湿重，过液氮，-70℃冰箱保存待测。实验前冰浴下用生理盐水将甲状腺制备成5％组织匀浆，3000转离心15分钟，留取上清待测。
3．检测指标①尿碘测定采用砷铈催化分光光度法。②抗氧化指标MDA测定采用TBA法；GSH-P_x测定采用谷胱甘肽过氧化物酶法；SOD测定采用黄嘌呤氧化酶法；H_2O_2测定采用钼酸胺法；组织蛋白测定采用考马斯亮兰法。试剂盒由南京建成生物工程研究所提供，按说明书操作。③甲状腺功能测定采用放射免疫方法检测大鼠血浆TSH，大鼠TSH试剂盒由英国Amersham公司提供；采用放射免疫方法检测大鼠血浆TT_4和TT_3(双抗法)，以及FT_3和FT_4(包被法)，试剂盒均由美国DPC公司提供。
结果
1.尿碘浓度与补水碘浓度呈显著正相关，普通动物和低碘动物的相关
系数分别为r二0.936和r二0.973。正常对照组的平均MUI为165.9叫犷L，
高碘I组平均MUI约为正常对照组的三倍左右，高碘n组平均MUI约为正
常对照组的六倍左右。低碘对照组尿碘MUI为19.2例扩L，低碘I组平均
MUI约为正常对照组的半倍，低碘n组平均MUI接近正常对照组的三倍。
2.低碘对照组甲状腺湿重和甲状腺相对重量均明显增大，补碘后(低’
碘I组和低碘n组)甲状腺湿重及甲状腺相对重量各时点较低碘对照组均
明显下降。而低碘I组和低碘n组间甲状腺湿重和甲状腺相对重量无明显
差异。普通动物三组间甲状腺湿重和甲状腺相对重量各时点均无明显差
异。
3.甲状腺GSH一Px活力在低碘I组1周时有短暂升高，此后随着补碘
时间延长，低碘I组和低碘n组甲状腺GSH一Px活力均呈现明显下降趋势，
分别在4周和2周后明显低于同期低碘对照组。低碘I组和低碘n组之间
甲状腺GSH一Px活力各时点均无显著性差异。高碘I组和高碘11组甲状腺
GSH一Px活力均在24周时低于同期正常对照组，而高碘I组和高碘n组之
间甲状腺GSH一Px活力各时点均无显著性差异。
4.与低碘对照组比较，低碘I组甲状腺SOD活力在1周时升高，此后
随着补碘时间延长，低碘I组和低碘11组甲状腺soD活力均呈现逐渐下降
趋势，在8周后明显低于同期低碘对照组。高碘I组、高碘n组和正常对照
组之间甲状腺SOD活力各时点均无显著性差异。
5.与低碘对照组比较，补碘后低碘I组和低碘11组甲状腺HZ 02含量
明显下降，各时点均明显低于低碘对照组。普通动物补碘后，高碘I组在2
周时低于正常对照组，高碘11组在1周时低于正常对照组，其他各时点均无
显著性差异。
6.与低碘对照组比较，补碘后低碘I组和低碘n组甲状腺MDA含量
明显下降，分别在2周和1周后低于同期低碘对照组。普通动物三组间，高
碘I组和高碘n组甲状腺MDA含量在1周时均低于同期正常对照组，其他
各时点则无显著性差异。
7.补碘1周时低碘I组和低碘n组GSH一Px/MDA明显升高，显著高于
同期低碘对照组，此后随着补碘时间延长而逐渐下降，低碘n组
GSH一/MDA在24周时显著低于同期低碘对照组。普通动物三个实验组
之间GsH一x/MDA各时点均无显著性差异。
8.碘缺乏使Wi妞大鼠血浆Tf.、F几水平明显降低，马H明显升高，补
充100叫扩L和330卜扩L浓度碘后，血浆代、叹水平明显升高，巧H明显降
低，Tl’3水平无明显变化，n、水平则在8周和/或24周时下降。
9.非碘缺乏wis往比大鼠补充300叫扩L和6团例扩L浓度碘后，血浆几
在1周和24周时低于正常对照组，盯3水平无明显变化，TLj几在1周和
(或)2周时低于同期正常对照组，TSH水平无明显变化。
结论
1.碘缺乏WIStar大鼠补充100叫犷L浓度碘后，甲状腺肿大得以部分恢
复，但未能恢复到正常甲状腺水平。同时甲状腺氧化损伤程度减轻，甲状腺
内抗氧化酶活力相应地下降，但甲状腺综合抗氧化防御能力并无下降，因此
碘缺乏大鼠补充100叫扩L浓度碘是安全的。
2.碘缺乏Wistar大鼠补充330叫犷L浓度碘后，甲状腺肿大得以部分恢
复，但未能恢复到正常甲状腺水平。同
To investigate the effect of chronic iodine excess on thyroid oxidative injury and antioxidation ability and thyroid function of Wistar rats fed with iodine deficient diet and normal diet originally. In order to ensure supplied iodine concentration being in the experimentation objectives, urinary iodine was inspected.
Methods
1. Group and treatment of experimental animals (1)Iodine deficient animal: 160 Wistar rats with 4 weeks old were fed with iodine deficient diet and double distilled water for three months to made iodine deficient goitrous model. Then 10 rats were killed, the remaining 150 rats were divided randomly into three groups: iodine deficient control group , iodine deficient I group and iodine deficient II group , which were fed with double distilled water, potassium iodate solutions with iodine concentrations as 100 and 330ug/L respectively. 10 rats of each group were killed at 1, 2, 4, 8 and 24 weeks after treatment. (2)Normal iodine intake animal: 150 Wistar rats, 4 weeks old, were fed with iodine sufficient diet and double distilled water for three months, then were divided randomly into three groups: normal control group , high iodine I group and high iodine II group , fed with double distilled water, potassium iodate solutions with i-odine concentrations as 300 and 660ug/L respectively. 10 rats of each g
roup were killed at 1, 2, 4, 8 and 24 weeks after treatment.
2. Animal sample collection and preparation (1) Urine: Rats were put in cage for one day with free access to food and water before killed in order to collect urine for 24 hours. Urine were then stored in refrigeration at - 20C. (2) Plasma: Rats were weighted and then anaesthetized by aether. Whole blood was
collected after cardiac puncture. Plasma was separated from blood by centrifu-ging at 3000 x g for 20 minutes and stored at - 20C. (3)thyroid homogenation: Thyroid were removed quickly after cardiac pumcture, weighted by electric balance , cooled in liquid nitrogen and stored at -70C. Thyroid were diluted with 0.9% sodium chloride to 5 percent thyroid homogenate and then centrifuged at 3000 x g for 15 minutes. The supernatant was collected for analysis.
3. Index determination (1)Urinary iodine: AS(III) - Ce4+ catalytic spectro-photometry method was used. (2)Index of antioxidation: MDA was determined by TBA method; GSH-PX was determined by glutathione peroxidase method; SOD was determined by xanthine oxidase method; H2O2 was determined by molybdate amine method; Tissue pretein was determined by Coomassie brilliant blue method. Kits were provided by Institute of Nanjing Jiancheng Biological Engineering. (3)Thyroid function: Radioimmunoassay was used to determined rats TSH whose kit was provided by Amersham company in UK. Radioimmunoassay was also used to determined TT4(double antibody method) and TT3(coat method) whose kits were purchased from DPC company in U. S. A.
Results
1. Concentration of urinary iodine was postivly relate to concentration of iodine supplied in water significantly. Correlation coefficient of normal iodine intake animals and iodine deficient animals was 0. 936 and 0. 973 respectively. Average of MUI was 165. 9ug/L in normal control group, while it was about three and six times in high iodine I group and high iodine II group respectively compared with normal control group. Average of MUI was 19. 2ug/L in iodine deficient control group while it was about half and three times in iodine deficient I group and iodine deficient II group respectively compared with normal control group.
2. Thyroid weight and thyroid relative weight in iodine deficient control group increased significantly. Thyroid weight and thyroid relative weight decreased obviously after iodine supplement in iodine deficient I group and iodine deficient II group as compared with those in iodine deficient control group. Thy-
roid weight and thyroid relative weight had no significant difference between iodine deficient I group and iodine deficient II group. There was also no significant difference among three groups
以基础是低碘摄入和正常碘摄入的两种碘营养状态的Wistar大鼠为研究对象，动态观察慢性轻中度碘过量对甲状腺氧化损伤和抗氧化能力的影响以及对甲状腺功能的影响，同时做尿碘监测，以保证所选用的碘浓度能符合试验目的的要求。
方法
1．实验动物分组和处理①低碘动物：4周龄Wistar大鼠160只饲以低碘饲料和双蒸水，三个月后复制出低碘甲肿模型，处死10只，剩余150只随机分为三组：低碘对照组、低碘Ⅰ组和低碘Ⅱ组。各组分别饲以双蒸水、含碘100μg／L和330μg／L的碘酸钾水。②普通动物：4周龄Wistar大鼠150只饲以普通饲料和双蒸水，三个月后随机分为三组：正常对照组、高碘Ⅰ组和高碘Ⅱ组。各组分别饲以双蒸水、含碘300μg／L和660μg／L的碘酸钾水。在给予处理因素的1、2、4、8、24周时分别处死大鼠，每次每组处死10只。
2．动物标本采集及制备①尿液：处死前一天将大鼠放入代谢笼中，自由进食及饮水，收集24小时尿液，-20℃冰箱中保存。②血浆：大鼠称体重，乙醚麻醉后，心脏采血，分离血浆，-20℃冰箱中保存。③甲状腺：大鼠经心脏采血处死后，迅速分离甲状腺，去除表面结缔组织，电子天平称湿重，过液氮，-70℃冰箱保存待测。实验前冰浴下用生理盐水将甲状腺制备成5％组织匀浆，3000转离心15分钟，留取上清待测。
3．检测指标①尿碘测定采用砷铈催化分光光度法。②抗氧化指标MDA测定采用TBA法；GSH-P_x测定采用谷胱甘肽过氧化物酶法；SOD测定采用黄嘌呤氧化酶法；H_2O_2测定采用钼酸胺法；组织蛋白测定采用考马斯亮兰法。试剂盒由南京建成生物工程研究所提供，按说明书操作。③甲状腺功能测定采用放射免疫方法检测大鼠血浆TSH，大鼠TSH试剂盒由英国Amersham公司提供；采用放射免疫方法检测大鼠血浆TT_4和TT_3(双抗法)，以及FT_3和FT_4(包被法)，试剂盒均由美国DPC公司提供。
结果
1.尿碘浓度与补水碘浓度呈显著正相关，普通动物和低碘动物的相关
系数分别为r二0.936和r二0.973。正常对照组的平均MUI为165.9叫犷L，
高碘I组平均MUI约为正常对照组的三倍左右，高碘n组平均MUI约为正
常对照组的六倍左右。低碘对照组尿碘MUI为19.2例扩L，低碘I组平均
MUI约为正常对照组的半倍，低碘n组平均MUI接近正常对照组的三倍。
2.低碘对照组甲状腺湿重和甲状腺相对重量均明显增大，补碘后(低’
碘I组和低碘n组)甲状腺湿重及甲状腺相对重量各时点较低碘对照组均
明显下降。而低碘I组和低碘n组间甲状腺湿重和甲状腺相对重量无明显
差异。普通动物三组间甲状腺湿重和甲状腺相对重量各时点均无明显差
异。
3.甲状腺GSH一Px活力在低碘I组1周时有短暂升高，此后随着补碘
时间延长，低碘I组和低碘n组甲状腺GSH一Px活力均呈现明显下降趋势，
分别在4周和2周后明显低于同期低碘对照组。低碘I组和低碘n组之间
甲状腺GSH一Px活力各时点均无显著性差异。高碘I组和高碘11组甲状腺
GSH一Px活力均在24周时低于同期正常对照组，而高碘I组和高碘n组之
间甲状腺GSH一Px活力各时点均无显著性差异。
4.与低碘对照组比较，低碘I组甲状腺SOD活力在1周时升高，此后
随着补碘时间延长，低碘I组和低碘11组甲状腺soD活力均呈现逐渐下降
趋势，在8周后明显低于同期低碘对照组。高碘I组、高碘n组和正常对照
组之间甲状腺SOD活力各时点均无显著性差异。
5.与低碘对照组比较，补碘后低碘I组和低碘11组甲状腺HZ 02含量
明显下降，各时点均明显低于低碘对照组。普通动物补碘后，高碘I组在2
周时低于正常对照组，高碘11组在1周时低于正常对照组，其他各时点均无
显著性差异。
6.与低碘对照组比较，补碘后低碘I组和低碘n组甲状腺MDA含量
明显下降，分别在2周和1周后低于同期低碘对照组。普通动物三组间，高
碘I组和高碘n组甲状腺MDA含量在1周时均低于同期正常对照组，其他
各时点则无显著性差异。
7.补碘1周时低碘I组和低碘n组GSH一Px/MDA明显升高，显著高于
同期低碘对照组，此后随着补碘时间延长而逐渐下降，低碘n组
GSH一/MDA在24周时显著低于同期低碘对照组。普通动物三个实验组
之间GsH一x/MDA各时点均无显著性差异。
8.碘缺乏使Wi妞大鼠血浆Tf.、F几水平明显降低，马H明显升高，补
充100叫扩L和330卜扩L浓度碘后，血浆代、叹水平明显升高，巧H明显降
低，Tl’3水平无明显变化，n、水平则在8周和/或24周时下降。
9.非碘缺乏wis往比大鼠补充300叫扩L和6团例扩L浓度碘后，血浆几
在1周和24周时低于正常对照组，盯3水平无明显变化，TLj几在1周和
(或)2周时低于同期正常对照组，TSH水平无明显变化。
结论
1.碘缺乏WIStar大鼠补充100叫犷L浓度碘后，甲状腺肿大得以部分恢
复，但未能恢复到正常甲状腺水平。同时甲状腺氧化损伤程度减轻，甲状腺
内抗氧化酶活力相应地下降，但甲状腺综合抗氧化防御能力并无下降，因此
碘缺乏大鼠补充100叫扩L浓度碘是安全的。
2.碘缺乏Wistar大鼠补充330叫犷L浓度碘后，甲状腺肿大得以部分恢
复，但未能恢复到正常甲状腺水平。同
To investigate the effect of chronic iodine excess on thyroid oxidative injury and antioxidation ability and thyroid function of Wistar rats fed with iodine deficient diet and normal diet originally. In order to ensure supplied iodine concentration being in the experimentation objectives, urinary iodine was inspected.
Methods
1. Group and treatment of experimental animals (1)Iodine deficient animal: 160 Wistar rats with 4 weeks old were fed with iodine deficient diet and double distilled water for three months to made iodine deficient goitrous model. Then 10 rats were killed, the remaining 150 rats were divided randomly into three groups: iodine deficient control group , iodine deficient I group and iodine deficient II group , which were fed with double distilled water, potassium iodate solutions with iodine concentrations as 100 and 330ug/L respectively. 10 rats of each group were killed at 1, 2, 4, 8 and 24 weeks after treatment. (2)Normal iodine intake animal: 150 Wistar rats, 4 weeks old, were fed with iodine sufficient diet and double distilled water for three months, then were divided randomly into three groups: normal control group , high iodine I group and high iodine II group , fed with double distilled water, potassium iodate solutions with i-odine concentrations as 300 and 660ug/L respectively. 10 rats of each g
roup were killed at 1, 2, 4, 8 and 24 weeks after treatment.
2. Animal sample collection and preparation (1) Urine: Rats were put in cage for one day with free access to food and water before killed in order to collect urine for 24 hours. Urine were then stored in refrigeration at - 20C. (2) Plasma: Rats were weighted and then anaesthetized by aether. Whole blood was
collected after cardiac puncture. Plasma was separated from blood by centrifu-ging at 3000 x g for 20 minutes and stored at - 20C. (3)thyroid homogenation: Thyroid were removed quickly after cardiac pumcture, weighted by electric balance , cooled in liquid nitrogen and stored at -70C. Thyroid were diluted with 0.9% sodium chloride to 5 percent thyroid homogenate and then centrifuged at 3000 x g for 15 minutes. The supernatant was collected for analysis.
3. Index determination (1)Urinary iodine: AS(III) - Ce4+ catalytic spectro-photometry method was used. (2)Index of antioxidation: MDA was determined by TBA method; GSH-PX was determined by glutathione peroxidase method; SOD was determined by xanthine oxidase method; H2O2 was determined by molybdate amine method; Tissue pretein was determined by Coomassie brilliant blue method. Kits were provided by Institute of Nanjing Jiancheng Biological Engineering. (3)Thyroid function: Radioimmunoassay was used to determined rats TSH whose kit was provided by Amersham company in UK. Radioimmunoassay was also used to determined TT4(double antibody method) and TT3(coat method) whose kits were purchased from DPC company in U. S. A.
Results
1. Concentration of urinary iodine was postivly relate to concentration of iodine supplied in water significantly. Correlation coefficient of normal iodine intake animals and iodine deficient animals was 0. 936 and 0. 973 respectively. Average of MUI was 165. 9ug/L in normal control group, while it was about three and six times in high iodine I group and high iodine II group respectively compared with normal control group. Average of MUI was 19. 2ug/L in iodine deficient control group while it was about half and three times in iodine deficient I group and iodine deficient II group respectively compared with normal control group.
2. Thyroid weight and thyroid relative weight in iodine deficient control group increased significantly. Thyroid weight and thyroid relative weight decreased obviously after iodine supplement in iodine deficient I group and iodine deficient II group as compared with those in iodine deficient control group. Thy-
roid weight and thyroid relative weight had no significant difference between iodine deficient I group and iodine deficient II group. There was also no significant difference among three groups
引文
1. WHO. Assessment of Iodine Deficiency Disorders and Monitoring their Elimination A guide for programme managers (second edition), WHO, unpublished document, 2001.
2．陈志祥，李忠之，许弘凯等．’97中国碘缺乏病监测．北京：人民卫生出版社，2000，3-21．
3．刘守军，孙树秋．1999年全国碘缺乏病监测资料汇总分析．中国地方病学杂志，2000，19(4)：269．
4．单忠艳，滕卫平，金迎等．碘致甲状腺功能减退症的流行病学对比研究．中华内分泌代谢杂志，2001，17(2)：71．
5. Mahmoud I, Colin I, Many M. C. et al. Direct toxic effect of iodide in excess on iodine- deficient thyroid glands: epithelial necrosis and inflammation associated with lipofuscin accumulation. [J]. Exp Mol Pathol, 1986, 44:259-271.
6. Li M, Boyages S. C. Iodide induced lymphocytic thyroiditis in the BB/W rat: evidence of direct toxic effects of iodide on thyroid subcellular structure.[J]. Autoimmunity, 1994,18:31 -40.
7. Bagchi N, Brown TR, Sundick RS. Thyroid cell injury is an initial event in the induction of autoimmune thyroiditis by iodine in obesestrain chickens. [J]. Endocrinology, 1995, 136(11) : 5054 -5060.
8. Many MC, Mestdagh C, van den Hove MF, et al. In vitro study of acute toxic effects of high iodide doses in human thyroid follicles. [J]. Endocrinology,1992, 131(2): 621-629.
9. Many MC, Papadopoulos J, Martin C, et al. Iodine induced cell damage in mouse hyperplastic thyroid is associated to lipid peroxidation. Progress in Thyroid Research, 1991, pp. 635-638,
10. Bagchi N, Brown TR, Herdegen DM, et al. Antioxidants delay the onset of thyroiditis in obese strain chickens. [J]. Endocrinology, 1990, 127 (4) :1590-1595.
11．李颖，王丹娜，陈秀洁．碘缺乏和碘过多对甲状腺形态和抗氧化能力的，
影响．中国地方病学杂志，2002，21(2)：91-93．
12．房辉，阎玉芹，陈祖培．缺碘与高碘大鼠甲状腺抗氧化能力的实验研究．中国地方病学杂志，2001，20(1)：11-13．
13．项建梅．不同剂量的碘的摄入对缺碘大鼠抗氧化能力的影响．中华医学会第六次全国内分泌学术会议汇编，2001年．
14．项建梅，陈祖培，邸红军等．高碘对小鼠抗氧化能力的影响．中国地方病学杂志，1999，18(4)：245-248．
15. Dunn JT, Dunn AD. Update on intrathyroidal iodine metabolism. [J]. Thyroid, 2001,11(5) : 407 -414.
16．吕社民．硒与甲状腺和甲状腺激素代谢．国外医学医学地理分册，1994，15(3)：97-101．
17. Corvilain B, Collyn L, van Sande J, et al. Stimulation by iodide of H_2O_2 generation in thyroid slices from several species. [J]. Am J Physiol Endocrinol Metab, 2000, 278(4) : E692 -699.
18. Ekholm R, Bjorkman U. Glutathione peroxidase degrades intracellular hydrogen peroxide and thereby inhibits intracellular protein iodination in thyroid epithelium. [J]. Endocrinology, 1997, 138 (7) : 2871 - 2878.
19. Prem Prakash Singh, Pradeep kumar G, Malini Laloraya. Regulation of superoxide Anion radical-superoxide dismutase system in the Avian thyroid by. TSH with reference to thyroid homonogenesis. [J]. Biochemical and Biophysical Research Communications, 1997,239 : 212-216.
20. Denef JF, Many MC, van den Hove M. F. Iodine -induced thyroid inhibition and cell necrosis: two consequences of the same free- radical mediated. mechanism? [J]. Mol Cel Endocrinology, 1996, 121:101-103.
21. Contempre B, Dumont JE, Denef JF, et al. Effects of selenium deficiency on thyroid necrosis, fibrosis and proliferation: a possible role in myxoedematous cretinism. [J]. Eur J of Endocrinology, 1995,133 : 99-109.
22. Vitale M, Matola TD, D'Ascoli F, et al. Iodide excess induces apoptosis in thyroid cells through a p53 -independent mechanism involving oxidative stress. [J]. Endocrinology, 2000,141 (2) : 598-605.
23. Hotz CS, Fitzpatricl DW, Trick KD, et al. Dietary iodine and selenium interact to affect thyroid hormone metabolism of rats. [J]. J. Nutr, 1997,
127：1214-1218．
24．赵克然，杨毅军，曹道俊等．氧自由基与临床．北京：中国医药科技出版社，1999，559
25. Mutaku JF, Poma J-F, Many M-C, et al. Cell necrosis and apoptosis are differentially regulated during goitre development and iodine- induced involution. [J]. J of Endocrinology, 2002,172:375 -386.
26. Allen EM. The effect of iodine on lipid peroxidation and ultrastructrue in the thyroids of BB/W rats. [J]. J of Endocrinological Investigation, 1992, 15: 519-523.
27．吴泰相，王家良．碘甲腺氨酸脱碘酶研究进展．中华内分泌代谢杂志，2000，16(3)：193-195．
28. Arther JR, Nicol F, Beckett GJ, et al. Selenium deficiency, thyroid hormone metabolism, and thyroid hormone deiodinases. Am J Clin Nutr, 1993,57 (Suppl) 236.
29. Pitsiavas V, Smerdely P, Li M, et al. Amiodarone induces a different pattern of ultastructural change in the thyroid to iodine excess alone in both the BB/W rat and the Wistar rat. [J]. European Journal of Endocrinology, 1997, 137:89-98.
30．房辉，阎玉芹，陈祖培．碘缺乏与碘过多对大鼠甲状腺肿形成及功能的影响．中国地方病学杂志，1999，14(3)：133-136．
2．陈志祥，李忠之，许弘凯等．’97中国碘缺乏病监测．北京：人民卫生出版社，2000，3-21．
3．刘守军，孙树秋．1999年全国碘缺乏病监测资料汇总分析．中国地方病学杂志，2000，19(4)：269．
4．单忠艳，滕卫平，金迎等．碘致甲状腺功能减退症的流行病学对比研究．中华内分泌代谢杂志，2001，17(2)：71．
5. Mahmoud I, Colin I, Many M. C. et al. Direct toxic effect of iodide in excess on iodine- deficient thyroid glands: epithelial necrosis and inflammation associated with lipofuscin accumulation. [J]. Exp Mol Pathol, 1986, 44:259-271.
6. Li M, Boyages S. C. Iodide induced lymphocytic thyroiditis in the BB/W rat: evidence of direct toxic effects of iodide on thyroid subcellular structure.[J]. Autoimmunity, 1994,18:31 -40.
7. Bagchi N, Brown TR, Sundick RS. Thyroid cell injury is an initial event in the induction of autoimmune thyroiditis by iodine in obesestrain chickens. [J]. Endocrinology, 1995, 136(11) : 5054 -5060.
8. Many MC, Mestdagh C, van den Hove MF, et al. In vitro study of acute toxic effects of high iodide doses in human thyroid follicles. [J]. Endocrinology,1992, 131(2): 621-629.
9. Many MC, Papadopoulos J, Martin C, et al. Iodine induced cell damage in mouse hyperplastic thyroid is associated to lipid peroxidation. Progress in Thyroid Research, 1991, pp. 635-638,
10. Bagchi N, Brown TR, Herdegen DM, et al. Antioxidants delay the onset of thyroiditis in obese strain chickens. [J]. Endocrinology, 1990, 127 (4) :1590-1595.
11．李颖，王丹娜，陈秀洁．碘缺乏和碘过多对甲状腺形态和抗氧化能力的，
影响．中国地方病学杂志，2002，21(2)：91-93．
12．房辉，阎玉芹，陈祖培．缺碘与高碘大鼠甲状腺抗氧化能力的实验研究．中国地方病学杂志，2001，20(1)：11-13．
13．项建梅．不同剂量的碘的摄入对缺碘大鼠抗氧化能力的影响．中华医学会第六次全国内分泌学术会议汇编，2001年．
14．项建梅，陈祖培，邸红军等．高碘对小鼠抗氧化能力的影响．中国地方病学杂志，1999，18(4)：245-248．
15. Dunn JT, Dunn AD. Update on intrathyroidal iodine metabolism. [J]. Thyroid, 2001,11(5) : 407 -414.
16．吕社民．硒与甲状腺和甲状腺激素代谢．国外医学医学地理分册，1994，15(3)：97-101．
17. Corvilain B, Collyn L, van Sande J, et al. Stimulation by iodide of H_2O_2 generation in thyroid slices from several species. [J]. Am J Physiol Endocrinol Metab, 2000, 278(4) : E692 -699.
18. Ekholm R, Bjorkman U. Glutathione peroxidase degrades intracellular hydrogen peroxide and thereby inhibits intracellular protein iodination in thyroid epithelium. [J]. Endocrinology, 1997, 138 (7) : 2871 - 2878.
19. Prem Prakash Singh, Pradeep kumar G, Malini Laloraya. Regulation of superoxide Anion radical-superoxide dismutase system in the Avian thyroid by. TSH with reference to thyroid homonogenesis. [J]. Biochemical and Biophysical Research Communications, 1997,239 : 212-216.
20. Denef JF, Many MC, van den Hove M. F. Iodine -induced thyroid inhibition and cell necrosis: two consequences of the same free- radical mediated. mechanism? [J]. Mol Cel Endocrinology, 1996, 121:101-103.
21. Contempre B, Dumont JE, Denef JF, et al. Effects of selenium deficiency on thyroid necrosis, fibrosis and proliferation: a possible role in myxoedematous cretinism. [J]. Eur J of Endocrinology, 1995,133 : 99-109.
22. Vitale M, Matola TD, D'Ascoli F, et al. Iodide excess induces apoptosis in thyroid cells through a p53 -independent mechanism involving oxidative stress. [J]. Endocrinology, 2000,141 (2) : 598-605.
23. Hotz CS, Fitzpatricl DW, Trick KD, et al. Dietary iodine and selenium interact to affect thyroid hormone metabolism of rats. [J]. J. Nutr, 1997,
127：1214-1218．
24．赵克然，杨毅军，曹道俊等．氧自由基与临床．北京：中国医药科技出版社，1999，559
25. Mutaku JF, Poma J-F, Many M-C, et al. Cell necrosis and apoptosis are differentially regulated during goitre development and iodine- induced involution. [J]. J of Endocrinology, 2002,172:375 -386.
26. Allen EM. The effect of iodine on lipid peroxidation and ultrastructrue in the thyroids of BB/W rats. [J]. J of Endocrinological Investigation, 1992, 15: 519-523.
27．吴泰相，王家良．碘甲腺氨酸脱碘酶研究进展．中华内分泌代谢杂志，2000，16(3)：193-195．
28. Arther JR, Nicol F, Beckett GJ, et al. Selenium deficiency, thyroid hormone metabolism, and thyroid hormone deiodinases. Am J Clin Nutr, 1993,57 (Suppl) 236.
29. Pitsiavas V, Smerdely P, Li M, et al. Amiodarone induces a different pattern of ultastructural change in the thyroid to iodine excess alone in both the BB/W rat and the Wistar rat. [J]. European Journal of Endocrinology, 1997, 137:89-98.
30．房辉，阎玉芹，陈祖培．碘缺乏与碘过多对大鼠甲状腺肿形成及功能的影响．中国地方病学杂志，1999，14(3)：133-136．
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