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表达人Fas配体的质粒用于治疗小鼠甲状腺相关眼病

Therapeutic application of plasmid DNA coding for human Fas ligand in animal model for thyroid-associated ophthalmopathy
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摘要 目的探求表达人Fas配体(hFasL)的质粒在甲状腺相关眼病(TAO)小鼠模型中的治疗作用。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(hTSHR)活化的脾细胞进行免疫,前者不予治疗,后者行眼球后注射表达hFasL的质粒pcDNA3.1(+)/hFasL。结果模型组52.6%的眼眶组织出现了肌纤维变性及溶解断裂、脂肪组织增生、水肿等TAO样改变,与对照组相比,TT4升高、TSH降低(P<0.05)。治疗组仅15.8%有类似TAO改变,电镜下见有凋亡细胞,TT4、TSH回复至对照组水平。TRAb在3组间均无差异。结论眼球后注射表达hFasL的质粒治疗TAO小鼠取得了一定效果。 Objective To investigate therapeutic application of eukaryotic expression vector pcDNA3. 1 ( + )/hFasL in animal model for TAO. Methods Animals in control group were immunized with splenocytes sensitized by blank plasmid pcDNA3.1 ( + ), and then treated with pcDNA3.1 ( + ). Animals in treated group and model group were all immunized with splenocytes sensitized by hTSHR, then the former were injected behind the eyeballs with pcD- NA3.1 ( + )/hFasL. Results In model group 52.6% animals displayed obvious edema, hyperplasia of adipose tissue, focal degeneration and disruption of muscular fibers in their orbital tissues, and when compared with the control group, elevated TT4 and reduced TSH levels (P 〈 0. 05 ) were also observed. In treatment group, only 15.8% showed changes of TAO with apoptosis was found, and there was no statistical significance in levels of TT4 and TSH between treated group and control group. TRAb level was not significantly different among the three groups. Conclusion Retrobulbar injection with the plasmid coding for hFasL has made a curative effect on TAO in mice. These results indicated the therapeutic potential of gene therapy via Fas/FasL - mediated pathway for TAO.
出处 《基础医学与临床》 CSCD 北大核心 2008年第11期1174-1177,共4页 Basic and Clinical Medicine
基金 重庆市卫生局重点科研项目(01-1-104) 重庆医科大学附属第一医院回国人员院内课题启动基金(2005-6)
关键词 格雷夫斯病 人Fas配体 疾病模型 动物 基因疗法 Graves' s disease human Fas ligand disease models, animal gene therapy
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参考文献12

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