【作者】 程刚；

【导师】 邓华聪；

【作者基本信息】 重庆医科大学 ， 内科学， 2012， 博士

【摘要】 目的：了解不同剂量放射性131I诱导甲状腺功能减退大鼠抑郁行为及脑内多巴胺受体1表达情况。方法：应用不同剂量（50μCi，100μCi，200μCi，400μCi）放射性131I处理健康Sprague-Dawley(SD)成年大鼠，获得成年甲状腺功能减退大鼠模型。于每两周测定血清T3，T4，TSH及体重，分别于第8周、12周行大鼠抑郁行为学实验：悬尾实验(Tail Suspension Test, TST)，强迫游泳实验(Forced Swim Test, FST)观察后处死，应用RT-PCR和Western blot方法观察脑纹状体D1DRmRNA及蛋白表达情况。结果：1.50μCi放射性131I并不能成功获得甲状腺功能减退大鼠模型，而100μCi以上放射性131I可以诱导成功建立甲状腺功能减退大鼠模型。2.甲状腺功能减退大鼠抑郁行为学实验(TST和FST)表明甲状腺功能减退大鼠抑郁行为明显，尤其是200μCi和400μCi组。3. RT-PCR结果表明在甲状腺功能减退时，脑纹状体D1DRmRNA表达是上调的，Western Blot实验结果与PCR结论一致，脑纹状体D1DR蛋白表达增加。结论：1.200μCi放射性131I是建立甲状腺功能减退大鼠模型的最佳剂量，2周后即可成功建立甲状腺功能减退大鼠模型。2.甲状腺功能减退大鼠有抑郁行为存在。3.大鼠甲状腺功能减退伴发抑郁与脑纹状体多巴胺受体1表达的上调有关。目的：了解甲状腺功能减退患者抑郁状态时SPECT脑多巴胺转运蛋白（DAT）显像。方法：18例因甲状腺癌行甲状腺全切术，拟行放射性碘-131治疗而停用左旋甲状腺素4-6周的继发性甲状腺功能减退患者与10例甲状腺功能正常的健康成人对照。分别行蒙哥马利抑郁量表（MADR）和汉密尔顿抑郁量表（HRSD）问卷，行99mTc-TRODAT-1多巴胺转运蛋白显像计算双侧纹状体与小脑的放射性比值(ST/CB)进行比较。结果：1.甲状腺功能减退组的MADRS和HRDS评分分别为19.44±8.07，19.83±7.49明显高于健康对照组（5.1±3.96，6.4±5.23），P值均<0.05。表明甲状腺功能减退病人存在明显抑郁。2.左右两侧纹状体/小脑比值（ST/CB）在正常对照组分别为1.61±0.05和1.615±0.06，在甲状腺功能减退组则分别为1.146±0.17和1.16±0.14，两组比较有明显统计学差异，提示甲状腺功能减退组两侧ST/CB比值明显降低。3.在正常对照组左右两侧ST/CB比值比较，P大于0.05，提示两侧ST/CB比值没有统计学差异。而甲状腺功能减退组左右两侧ST/CB比值比较，P小于0.05，提示在甲状腺功能减退组两侧分布均有统计学差异。结论：1.甲状腺功能减退病人MADRS和HRDS抑郁量表评分均高于正常对照组，说明甲减伴发抑郁。2.甲状腺功能减退伴发抑郁时双侧纹状体与小脑的放射性比值（ST/CB）明显降低，表明多巴胺转运蛋白表达降低，提示脑纹状体多巴胺功能降低参与甲状腺减退伴抑郁的发病。更多还原

【Abstract】 Objective: To observe depression behavior and striatal dopamine type-1receptor(D1DR) expression in hypothyroidism rats induced by different dose ofradioiodine-131.Methods: Sprague-Dawley (SD) rats were treated with four different dosees ofradioiodine-131which were50μCi,100μCi,200μCi,400μCi respectively to get theadult hypothyrodisim rat models. Serum T3, T4and TSH and weights were measuredevery two weeks. Tail Suspension Test (TST) and Forced Swim Test (FST) were done atthe8th week and12cond week after radioiodine treatment to evaluate the depressivebehavior of the rats, and all the rats were killed after depressional experiments had beendone. D1DR expressions were determined by RT-PCR and West Blot.Results: We didn’t get adult hypothyroidism models with50μCi radioiodine. Wesuccessful got hypothyroidism models with100μCi or more than100μCi radioiodine.TST and FST results indicated that hypothyroidism rats with obvious depressionbehaviors especially in200μCi and400μCi groups. RT-PCR results indicated thatD1DR mRNA in stratum were upregulated in hypothyroidism rats. Striatal D1DR protein were increased with Western Blot assay.Conclusions:200μCi is an optimal dose for rat hypothyroidism model, and it onlytakes2weeks to successfully get the hypothyroidism models. Depressional behaviorsinduced by hypothyroidism, and this depression is associated with the upregulation ofD1DR in striatum. Objective: To study brain stiatal dopamine transporters (DAT) SPECT imagingand depression in hypothyroidism patients.Methods:18thyroid cancer patienst who had received total thyroidectomy andL-thyroxin were retreated for4-6weeks as the prepareation for radioiodine treatment asthe hypothyroidism patients and10healthy volunteers as control subjects were selected.Depression states in all the subjects were measured byHamilton Depression Rating Scale for Depression (HRSD) and Montgomery-sbergDepression Rating Scale (MADRS). Dopamine transporters (DAT) SPECT imagingswere conducted with99mTc-TRODAT-1. Bilateral striatum DAT specific uptakes of99mTc-TRODAT-1were calculated by the ratio of DAT uptake in striatum (ST) andcerellum (CB).Results: MADRS and HRDS scores which were19.44±8.07and19.83±7.49respectively in hypothyroidism were significant higher than contral subjects which were 5.1±3.96and6.4±5.23respectively(P<0.05). These results indicated that obviousdepression in hypothyroism. The ratio of ST/CB in the right and left striatum were1.61±0.05and1.615±0.06respectively in control subjects, which is significant higherthan hypothyroidism patients which were1.146±0.17and1.16±0.14respectively(P<0.05). The ratio of ST/CB had significant difference between the rightand left striatum in hypothyroidism patients (P<0.05), but no significant difference inthe control subjects (P>0.05).Conclusions: MADRS and HRDS scores in hypothyroidism are higher thancontrol subjects, and this indicates obvious depression in hypothyroidism. The ratio ofST/CB in bilateral striatum decreases in hypothyroidism patients, and this indicates thatDAT expressing decreased. Dopamine system function in brain striatum decreasingtakes part in the mechanism of depression in hypothyroidism.更多还原