摘要
目的:采用人类促甲状腺激素(hTSH)刺激及放射性碘-131(131I)注射Wistar大鼠的方法,建立甲状腺功能减低(甲减)及其甲状腺相关眼病(TAO)的动物模型。方法:将20只Wistar大鼠随机分为实验组和正常组,实验组大鼠腹腔内注射hTSH。第8周腹腔内注射131I,根据不同剂量将实验组分为低剂量组(A组)、中剂量组(B组)及高剂量组(C组)。第16周后处死所有大鼠,机械分离甲状腺,取眼眶组织做病理学观察,采用常规HE染色方法,观察和分析大鼠眼眶内的病理学变化。用电化学发光法测定血清FT3和FT4,酶联免疫吸附法测大鼠血清促甲状腺素(rTSH)和TRAb水平。结果:131I注射后8周,大鼠血清FT4水平A组(16.98±2.92)pmol/L、B组(1.84±0.44)pmol/L和C组(1.35±0.37)pmol/L均降低,三组与正常组(D组)比较差异均有显著性(P<0.05);且C组和B组明显低于A组,差异有显著性(P<0.05);血清rTSH水平C组(2.53±0.10)mIU/L、B组(2.37±0.32)mIU/L略高于D组(2.17±0.38)mIU/L,A组(1.78±0.36)mIU/L略低于D组,但差异均无显著性(P>0.05);A组血清TRAb(4.69±1.52)IU/ml和B组(4.49±2.60)IU/ml水平明显低于D组12.79±0.75)IU/ml,而C组血清TRAb(10.36±4.48)IU/ml与D组比较无明显差异(P>0.05)。眼眶组织学观察,实验组出现眼眶组织黏液变性、水肿,眼肌水肿以及肥大细胞为主的浸润,细胞间隙明显增宽。随着131I剂量的增加,B和C组出现脂肪组织和纤维组织增生,肌纤维变性断裂,肌细胞核肥大变性,眼眶血管扩张,C组肌纤维甚至有空泡形成。结论:采用hTSH刺激和131I注射制作的动物模型具有甲减及TAO的普遍特征,并证实甲减伴有TAO的存在,方法简便易行,不仅可用于131I治疗后甲减基础研究的需要,也可作为对其他原因所致甲减或TAO机制探索的模型。
Objective To establish an animal model for hypothyroidism and thyroid-associated ophthalmopathy（TAO） by method of the human thyrotropin（hTSH） stimulus and radioactive iodine-131（131I） injection in Wistar rats.Methods Twenty Wistar rats were divided randomly into experimental group and normal group（group D）,the experimental group were injected intraperitoneally with hTSH 8 weeks of intraperitoneal injection 131I,based on different dosage of 131I,experiments groups were divided into low-dose group（group A）,medium dose group（Group B） and the high-dose group（Group C）.All rats were sacrificed at weeks 16 for histology,thyroid and orbital tissue were isolated,observation and analysis of pathological changes in rat orbit with routine HE staining.Serum FT3and FT4levels were detected by electro chemiluminescence,serum rat TSH（rTSH） and TRAb levels measured by ELISA.Results After eight weeks of injection 131I,serum FT4 level in group A（16.98±2.92） pmol/L,group B（1.84± 0.44） pmol/L and group C（1.35± 0.37） pmol/L are reduced,three groups and normal group（group D）differences were significant（P0.05）;group A（1.78±0.36） mIU/L is slightly lower than group D,but also no significant difference（P〉0.05）.Serum TRAb level in group A（4.69±1.52）IU/ml and group B（4.49±2.60）IU/ml was significantly lower than that in group D（12.79±0.75）IU/ml,the difference was significant（P〉0.05）.group C（10.36±4.48）IU/ml and group D was no significant difference（P〉0.05）.Histological observation in orbital tissues,experimental groups displayed edema and mucinous degeneration,intercellular space widening significantly,mast cell infiltration in most of rats.With increasing doses of 131I,group B and group C showed proliferation of adipose tissue and fibrous tissue,degeneration and disruption of muscular fibers,muscle fiber fracture,orbital vascular dilatation,the muscle cell nucleus hypertrophy.The vacuole formation appeared in muscle fibers were found in group C.In group D,orbital tissues were normal histologically.Conclusion The animal model constructed by hTSH stimulus and131I injection produced general characteristics of hypothyroidism and TAO.And confirmed the presence of hypothyroidism associated with TAO.The method is simple and to utilize not only for fundamental research of hypothyroidism after 131I treatment,but also as a model to explore other reasons caused hypothyroidism or the TAO mechanism.
出处
《放射免疫学杂志》
CAS
2012年第5期490-492,共3页
Journal of Radioimmanology
基金
上海市普陀区卫生系统自主创新科研资助项目(普科委[2008]32号)
