Graves病动物模型干预模式的探讨

Effects of time and immunization on the animal model of Graves′ disease

目的研究造模时间及免疫次数对促甲状腺激素受体(TSHR)A亚单位的重组腺病毒(Ad-TSHR289)诱导的毒性弥漫性甲状腺肿(Graves病)模型的影响。方法 45只BALB/c小鼠分别注射对照腺病毒(Ad-Lacz)或AdTSHR289,于第2次免疫后2周或第3次免疫后4周处死。所有小鼠均采取摘眼球取血,放免法检测血清促甲状腺激素受体抗体(TRAb)以及总甲状腺素(TT4)水平;剥离甲状腺,进行组织学检查。结果所有注射Ad-TSHR289的小鼠相对于对照组TRAb均明显升高;5周-造模组、10周-造模组的Graves病发病率分别为56%(9/16)、75%(9/12);10周-造模组甲状腺组织学改变与TT4水平变化吻合度为100%,相对于5周-造模组的50%(8/16)明显升高。结论 10周-造模组相对于5周-造模组具有发病率高、组织学改变与血清TT4水平吻合度高等优势;造模时间以及免疫次数均对该Graves病模型有着较大的影响。

Objective To investigate the effects of time and immunization frequency of administration of Ad- TSHR289 on the development of a Graves＇ disease （GD） animal model. Methods BALB/c mice were injected with Ad-TSHR289 or Ad-lacz twice （5 week） or thrice （10 week） at three-weekly intervals. Blood and thyroid glands were obtained 2 weeks or ~ weeks after iniection. Total thyroxine （TT4） and thyrotropin receptor autoantibody （TRAb） levels were measured by radioimmutaoassay （RIA）. Results TRAb significantly increased in all the mice injected with Ad-TSHR289 compared with the controls. The incidence of GD was 56% （9/16） in 5- week model group and 75% （9/12） in 10-week model group. The consistency between serum TT4 level and histological changes of the thyroid was 50% in 5-week model group and 100% in 10-week model group, respectively. Conclusion Ten-week intervention is more effective than 5-week one in inducing a GD animal model. Intervention time and immunization frequency are two important factors affecting the development of a GD animal model induced by Ad-TSHR289.