放射性^(131)Ⅰ诱导的甲状腺功能减退大鼠模型的构建  

Establishment of an animal model of radioactive ^(131)Ⅰ-induced hypothyroidism in rats

作　　者：战莹 武晓丹 郝珊瑚 Zhan Ying;Wu Xiaodan;Hao Shanhu(General Hospital of Northern Theater Command,Shenyang 110016,Liaoning Province,China)

机构地区：[1]北部战区总医院,辽宁省沈阳市110016

出　　处：《中国组织工程研究》2023年第17期2631-2636,共6页Chinese Journal of Tissue Engineering Research

摘　　要：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^(131)Ⅰ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^(131)Ⅰ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^(131)Ⅰ前、注射^(131)Ⅰ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^(131)Ⅰ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组大鼠血清促甲状腺激素浓度在4,8,12,16周逐渐升高,FT3、FT4水平逐渐下降(P<0.05);12.95 MBq、18.5 MBq组大鼠丙氨酸氨基转移酶、碱性磷酸酶水平高于对照组,18.5 MBq组尿素氮、肌酐水平较对照组升高(P<0.05);②注射^(131)Ⅰ前,各组甲状腺清晰显影,靶/非靶比值无显著差异(P>0.05);与对照组相比,第4周9.25 MBq、12.95 MBq、18.5 MBq组甲状腺未见显影,靶/非靶比值减小(P<0.05),且在8,12,16周随访均未显影,但各剂量组之间靶/非靶比值差异无显著性意义(P>0.05);注射^(131)Ⅰ后大鼠甲状腺滤泡体积变小、萎缩,部分呈不规则形态;③结果表明,采用腹腔注射9.25 MBq剂量^(131)Ⅰ,且该剂量在4周内可使大鼠成功建立稳定的甲状腺功能减退模型,该研究为核医学^(131)Ⅰ治疗领域动物模型的建立提供参考。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 radioactive ^(131)Ⅰ 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 MBq ^(131)Ⅰ 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 before ^(131)Ⅰ injection,4,8,12,and 16 weeks after injection of ^(131)Ⅰ.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 by ^(131)Ⅰ 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 before ^(131)Ⅰ 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

关 键 词：^(131)Ⅰ 大鼠 甲状腺功能减退症 单光子发射计算机断层成像术 FT3 FT4 丙氨酸氨基转移酶 碱性磷酸酶 尿素氮 肌酐 

分 类 号：R459.9[医药卫生—治疗学] R496[医药卫生—临床医学] R318