放射性131Ⅰ诱导的甲状腺功能减退大鼠模型的构建

背景：目前，甲状腺功能减退动物模型造模过程中动物及药物剂量的选择各有差异，造模成功与否的标准也未得到统一。目的：探讨放射性¹³¹Ⅰ诱导大鼠甲状腺功能减退模型的可行性和最佳剂量。方法：健康雄性SD大鼠40只，随机分为5组，每组8只。其中4组大鼠分别腹腔注射4.625,9.25,12.95,18.5 MBq ¹³¹Ⅰ溶液，构建甲状腺功能减退模型；另一组大鼠为正常对照组注射等量生理盐水。分别于注射¹³¹Ⅰ前、注射¹³¹Ⅰ后4,8,12,16周测量大鼠体质量变化，采用ELISA试剂盒法分别测定血清中促甲状腺激素、FT3、FT4、丙氨酸氨基转移酶、门冬氨酸氨基转移酶、碱性磷酸酶、尿素氮、肌酐、尿酸水平，通过甲状腺¹³¹Ⅰ静态显像评价甲状腺功能，苏木精-伊红染色观察甲状腺组织形态学改变。结果与结论：(1)与对照组相比，第8,12,16周9.25 MBq、12.95 MBq、18.5 MBq组大鼠体质量下降(P <0.05);9.25 MBq、12.95 MBq、18.5 MBq组大鼠...

Establishment of an animal model of radioactive131I-induced hypothyroidism in rats

BACKGROUND: Up to now, there is no unified conclusion on the selection of animals and drug doses and the criteria for successful modeling in the modeling process of hypothyroid animal models. OBJECTIVE: To explore the feasibility and optimal dose of radioactive131I in the establishment of hypothyroidism model in rats METHODS: Forty healthy male Sprague-Dawley rats were randomly divided into five groups (n=8 per group). Four groups were injected intraperitoneally with 4.625, 9.25, 12.95, and 18.5 MBq131I solution to construct hypothyroidism models and the control group was injected with the same amount of normal saline. The body mass of rats was measured before131I injection, 4, 8, 12, and 16 weeks after injection of131I. The serum levels of thyroid-stimulating hormone, free triiodothyronine, free thyroxine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine, and uric acid were determined by an ELISA kit. Thyroid function was evaluated by131I static imaging and morphological changes of thyroid tissue were observed by hematoxylin-eosin staining. RESULTS AND CONCLUSION: Compared with the control group, the body mass of the rats in the 9.25, 12.95, and 18.5 MBq groups were significantly decreased at 8, 12, and 16 weeks (P < 0.05). The serum thyroid-stimulating hormone concentration gradually increased in the 9.25, 12.95, and 18.5 MBq groups at 4, 8, 12, and 16 weeks, while the levels of free triiodothyronine and free thyroxine gradually decreased (P < 0.05). The levels of alanine aminotransferase and alkaline phosphatase in the 12.95 and 18.5 MBq groups were significantly higher than those in the control group, while the blood urea nitrogen and creatinine levels in the 18.5 MBq group were significantly higher than those in the control group (P < 0.05). The thyroid glands in each group were clearly visualized before131I injection, and the target-to-nontarget ratio was not significantly different among groups (P > 0.05). Compared with the control group, the thyroid glands of the 9.25, 12.95, and 18.5 MBq groups were not visualized in the 4th week and the target-to-nontarget ratio was significantly decreased (P < 0.05). The thyroid glands were undeveloped at the 8-, 12-, and 16-week follow-up visits, but there was no statistical difference in the target-to-nontarget ratio among groups (P > 0.05). After injection of131I, the thyroid follicles of rats became smaller and shrunken, and some of them were irregular. All these findings indicate that intraperitoneal injection of131I at a dose of 9.25 MBq could successfully establish a stable hypothyroid model in rats within 4 weeks, which provide a reference for the establishment of animal models in the field of nuclear medicine131I therapy. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.