Study On The Effect Of Sustained Excess Iodine Intake On The Function Of Thyroid ^99mTc-pertechnetate Uptake And The Exploration On Mechanism In Rats

Objective:To study the effect of sustained excess iodine intake on the function of thyroid ^99mTc-pertechnetate uptake and explore the related molecular mechanism in rats.Methods:150 male Wistar rats were randomly divided into normal iodine group?group NI,n=30,iodine 10?g/d?and high iodine group?group HI,n=120?.Rats in group HI were administrated potassium iodate?KIO₃?by means of intragastric,Rats in NI group were administrated with same amount of distilled water.According to different high iodine concentration,group HI was divided into 4 groups:group 10 HI,50 HI,100 HI and 500 HI?each group n=30,iodine 100?g/d,500?g/d,1000?g/d,5000?g/d,respectively?.After a 7-day high-iodine diet,each group was randomly divided into 3subgroups?each group n=10?:7 days group?rats in the group were executed after the diet?,10 days group?rats in the group went on with a limit iodine intake for 3 days,then the rats were executed?,14 days group?rats in the group went on with limit iodine intake for 7 days,then the rats were executed?.All rats were given 1.85 MBq^99mTcO₄^-?50?Ci?,then thyroid glands of the rats were isolated,weighed and the ^99mTc-pertechnetate uptake rate?%ID/g?of thyroid gland for each sample was calculated in 20 minutes.Sodium-iodide symporter?NIS?expression level was analyzed by using Western blot.Thyroid apoptosis index?AI?was observed by TUNEL,B-cell lymphoma/leukemia-2?Bcl-2?protein,Bcl-2 Assaciated X protein?BAX?and caspase-3 expression were measured by immunohistochemistry.One-way ANOVA or Welch test was used to compare the differencesamong groups.Multiple comparisons were performed by LSD or Tamhane'T2method.The correlationsamong the indexes were analyzed by Spearman's rank correlation test.A value of p<0.05 was considered as statistically significant.Results:The results showed that in the 7 days group,10 days group and 14 days group,%ID/g among different iodine concentration groups were all different and these differences were statistically significant?F=52.195,106.979,48.825,respectively,p<0.001?.%ID/g decreased when the concentration of iodide increased.In NI and 10 HI groups,there were no significant differences among different time groups??F=0.542,3.268,p=0.588,0.054?,respectively?.In 50 HI,100 HI and 500 HI groups,significant differences were found among time groups?F=37.292,90.408,10.442,respectively,p<0.001?,and%ID/g increased over iodine-limited time.Western blot analyses of NIS indicated that in 7 days group,10 days group and 14 days group,NIS among different iodineconcentrationgroupsallhavestatisticallysignificantdifferences?F=93.948,119.219,72.020,respectively,p<0.01?,and NIS decreased when the concentration of iodide increased.In NI and 10 HI groups,there were no significant difference among different time groups(?F=0.090,4.753,p=0.915,0.058;respectively?.In 50 HI,100 HI and 500 HI groups,statistically significant differences were found among different time groups?F=13.922,11.714,14.882,p=0.006,0.008,0.005,respectively?.Immunohistochemistry score of NIS showed that in 7 days group,10days group and 14 days group,differences among iodine concentration groups were all statistically significant?F=14.818,14.627,18.530,respectively,p<0.01?.And there were no significant differences in the immunohistochemistry score of NIS in different time groups when the iodine concentration was the same.Immunohistochemistry score results of AI and apoptosis related protein showed that in 7 days group,10 days group and 14days group,differences of AI,BAX,Bcl-2 and Caspase-3 protein among different iodine concentration groups wereall statistically significant?F?AI?=471.981,675.434,531.097.p<0.001;F?BAX?=443.940,718.864,707.327,p<0.001;F?Bcl-2?=62.532,75.889,50.918,p<0.001;F?Caspase-3?=84.114,113.141,62.218,p<0.001?.And with the increasing of iodide concentration,the protein levels of AI,BAX and Caspase-3expression increased,but Bcl-2 protein decreased.And there were no significant differences in the AI,BAX,Bcl-2 and Caspase-3 in different time groups when the iodine concentration was the same.Spearman correlation analysis showed that there was a significantly negative correlation?r=-0.853,-0.826,-0.942,p<0.01?between the concentration of iodine and%ID/gNIS protein and Bcl-2;and there was a significantly positive correlationbetween the concentration of iodine and AI,BAX,Caspase-3?r=0.945,0.941,0.939,respectively,p<0.01?,separately.There was a significant positive correlation between%ID/g and NIS,Bcl-2protein,?r=0.726,0.863,respectively,p<0.01?,separately;and there was a significantly negative correlation between%ID/g and AI,BAX,Caspase-3?r=-0.779,-0.864,-0.887,respectively,p<0.01?,separately.Conclusion:Sustained excess iodine intake can inhibit thyroid uptake of ^99mTcO₄^-in rats,the mechanism is associated with the down-regulation of the NIS protein expression.Sustained excess iodine intake can promote the apoptosis of thyroid cells by up-regulating BAX and Caspase-3 protein and down-regulating the Bcl-2protein in rats,and then promotes apoptosis of rat throid cells.There is a correction between thyroid uptake of^99mTcO₄^-and apoptosis.The results suggest that iodine's intake should be restricted for a few days before ^99mTcO₄^-thyroid scan and the time is determined by the different iodine intake levels.