实验性甲状腺功能亢进大鼠脑多巴胺转运蛋白及多巴胺含量的变化

目的研究甲状腺激素升高时脑纹状体多巴胺转运蛋白（DAT）、多巴胺（DA）及其代谢产物3，4二羟苯乙酸（DOPAC）的含量变化。方法将24只大鼠分为2组，其中一组采用灌胃法连续每天给予大鼠左甲状腺素钠（优甲乐，用量按大鼠体质量25μg／100g，溶于生理盐水中，体积1ml）造成实验性大鼠甲状腺激素增高状态；对照组仅采用灌胃法给予生理盐水1ml；于模型建立前后按随机数字表法抽取左甲状腺素钠组及对照组大鼠各6只，分别取尾静脉血1ml，采用放射免疫法测定TT3及，TT4水平。14d后将上述对照组及左甲状腺素钠组大鼠再各自平均分为2组，一组用于99^Tc^m-2β-N，N’-双（2-巯乙基）乙撑二胺基]甲基-3β-（4-氯苯基）托烷（TRODAT-1）大鼠脑内分布研究，另一组用于高效液相-电化学检测器（HPLC-ECD）测纹状体DA及DOPAC含量，观察上述大鼠脑纹状体区DAT的分布及DA、DOPAC含量的变化。多组比较采用ANOVA分析，2组间比较采用均数t检验。结果左甲状腺素钠组大鼠在服用左甲状腺素钠后活动明显增加，体质量增长低于正常对照组（223．90±8．40）与（261．60±14．20）g，t=6．98，P〈0．05]。甲状腺激素水平测定示：左甲状腺素钠组给药前后TT3，分别为（1．46±0．17）和（2．72±0．29）nmol／L（t=10．51，P〈0．0001）；TT4分别为（83．52±10．06）和（187．12±36．48）nmol／L（t=7．74，P〈0．0001）；对照组生理盐水注射前后TT3分别为（1．54±0．09）和（1．71±0．20）nmol／L（t=1．68，P〉0．05），TT4分别为（98．38±9．77）和（88．38±6．76）nmol／L（t=1．36，P〉0．05）。99^Tc^m-TRODAT-1大鼠脑内分布（每克脑组织百分注射剂量率，％ID／g）研究示：左甲状腺素钠组纹状体为（2．80±0．25）％ID／g，明显低于正常对照组（3．13±0．14）％ID／g，t=-3．62，P〈0．05]。经检测左甲状腺

Change of striatum dopaminergic transporter and content of dopamine in rats with experimental hyperthyroidism

Objective The central dopamine system plays an important role in regulating movementand mood.In our routine clinical practice,we found that patients with hyperthyroidism often show tremor oftheir hands or legs.Meanwhile they also experienced emotional problems such as anxiety and depression.These reminded us that there might be close relationship between thyroid hormone and dopamine system.Based on our previous works,in this study we evaluated the change of striatum dopamine transporter(DAT)by using 99Tcm-2β-N,N'-bis(2-mereaptoethyl)ethylenediamino]methyl,3β-(4-chlorophenyl)tropane (TRODAT-1) brain biodistribution,and the content of striatum dopamine and its metabolites 3.4-di-hydroxyphenylacetic (DOPAC)by high performace liquid chromatograph-electrochemical detection(HPLC-ECD)in rats with experimental hyperthyroidism.Methods All 24 rats were randomly divided into two groups,thyroxin group were induced by daily thyroxin infusion for 14d to be experimental hyperthyroidism,the others were control group which received saline infusion.The blood samples were randomly taken from thyroxine group and control group,and the concentration of Tr3 and 13"4 were detected by radioimmunoas-say.After 14 d,both experimental (thyroxine group) and control group were further divided into 2 sub-groups.One was for evaluation of the function of striatum DAT by 99Tcm-TRODAT-1 biodistribution study and the other was for HPIJC-ECD measurement of the concentration of dopamine and its metabolites DOPAC.Results Significantly hyperactivity and weight loss(223.90±8.40)VS(261.60±14.20)g,t=6.98.P<0.05] in thyroxin than control groups were observed.Of the thyroxin group.the concentration of TT3 and TT4 after thyroxin infusion was significantly elevated than that of before thyroxin infusion(2.72±0.29)V8(1.46±0.17)nmol/L,t=10.51,P<0.0001.and (187.12±36.48) vs (83.52±10.06)nmol/L,t=7.74,P<0.0001].Of the control group,the concentration of TT3,and TT4 after saline infu-sion showed no statistical significance as compared with before saline infusion (1.71±0.20) vs (1.54±O.09)nmol/L,t=1.68.P>0.05 and(88.38±6.76) vs (98.38±9.77)nmol/L.t=1.36.P>O.05].For 99Tcm-TRODAT-l brain biodistribution(the percent injection dose of per gram of tissue,%ID/g),the striatum of thyroxin group was(2.80±0.25)%ID/g,lower than that of the control group (3.13±0.14)%ID/g,t=-3.62,P<0.05].The content of striatum DA was(12 109.30±629.20)ng/g brain tissue,higher than that of the control(9012.00±318.80)ng/g brain tissue,t=10.76.P<0.000l 1],the content of DOPAC Was(1079.3±97.00)ng/g brain tissue,higher than that of the control(873.20±67.50)ng/g brain tissue,t=4.27.P<0.05].Conclusions Decreased 99Tcm-TRODAT-1 uptake was ob-served in striatum DAT during rats with experimental hyperthyroidism.The possible reason might be due to the increased dopamine binding with DAT.