表达人Fas配体的质粒治疗Graves病模型小鼠

Therapeutic application of plasmid DNA coding for human Fas ligand in animal model of Graves disease

目的:观察表达人Fas配体的质粒治疗Graves病模型小鼠的效果。方法:小鼠分为3组。对照组(10只)用空质粒pcDNA3.1(+)活化的脾细胞免疫后,以空质粒治疗;模型组和治疗组(各19只)均以人TSH受体(Human thyrotropin receptor,hTSHR)活化的脾细胞进行免疫,前者不予治疗,后者甲状腺注射表达hFasL的质粒pcDNA3.1(+)/hFasL。结果:模型组47.4%的甲状腺细胞出现增生、肥大,以及甲状腺滤泡腔胶质减少,与对照组相比,TT4、TRAb升高、TSH降低(P<0.05)。治疗组仅15.8%有类似甲状腺功能亢进改变,电镜下见细胞核异染色质边集,TT4、TSH、TRAb回复至对照组水平。结论:表达人Fas配体的质粒治疗Graves病模型小鼠取得一定效果。

Objective： To observe therapeutic effects of plasmid pcDNA3.1/hFasL on mice with Graves＇ disease. Methods： Three groups were set in this study. Animals in the control group （10 mice） were immunized with splenocytes sensitized by blank plasmid pcDNA3.1 （＋）, and then treated with pcDNA3.1 （＋）. Animals in the model group （19 mice ） and treated group （19 mice ） were all immunized with splenocytes sensitized by hTSHR, then the latter were injected with pcDNA3.1 （ ＋ ）/hFasL. Results ： 47.4%of thyroid follicular epithelia in the model group displayed hypertrophy and hyperplasia, and the follicles cavity contained little colloid. Compared with the control group, elevated TT4 and TRAb and reduced TSH levels（P〈0.05 ） were also observed in the model group. In the treated group, only 15.8% of thyroid follicular epithelia showed pathologic changes of GD with heterochromatin margination. There was no statistical significance in the levels of TT4 , TRAb, and TSH between the treated group and the control group. Conclusion： Gene therapy by administration of plasmid pcDNA3.1/hFasL has made a curative therapeutic effects on Graves＇ disease in animal model.