基础医学与临床 ›› 2008, Vol. 28 ›› Issue (11): 1174-1177.

• 研究论文 • 上一篇    下一篇

表达人Fas配体的质粒用于治疗甲状腺相关眼病小鼠

李秀娟 刘纯 张徽 随华 詹升华   

  1. 重庆医科大学附属第一医院内分泌科 重庆医科大学附属第一医院内分泌科 重庆医科大学 附属第一医院 内分泌科 重庆医科大学附属第一医院内分泌科 重庆医科大学附属第一医院内分泌科
  • 收稿日期:2007-07-09 修回日期:2008-01-18 出版日期:2008-11-25 发布日期:2008-11-25
  • 通讯作者: 刘纯

Therapeutic application of plasmid DNA coding for human Fas ligand in animal model for thyroid-associated ophthalmopathy

Xiu-juan LI, Chun LIU, Hui ZHANG, Hua SUI, Sheng-hua ZHAN   

  1. Dept. Endocrinology, the First Affiliated Hospital of Chongqing University of Medical Sciences Dept. Endocrinology, the First Affiliated Hospital of Chongqing University of Medical Sciences Dept. Endocrinology, the First Affiliated Hospital of Chongqing University of Medical Sciences Dept. Endocrinology, the First Affiliated Hospital of Chongqing University of Medical Sciences Dept. Endocrinology, the First Affiliated Hospital of Chongqing University of Medical Sciences
  • Received:2007-07-09 Revised:2008-01-18 Online:2008-11-25 Published:2008-11-25
  • Contact: Chun LIU,

摘要: 目的 探求表达人Fas配体(human Fas ligand, hFasL)的质粒在甲状腺相关眼病(thyroid-associated ophthalmopathy, 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(human thyrotropin receptor, 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。

Abstract: Objective To investigate therapeutic application of eukaryotic expression vector pcDNA3.1(+)/hFasL in animal model for TAO. Methods Three groups were set in this study. Animals in control group (10 mice) were immunized with splenocytes sensitized by blank plasmid pcDNA3.1(+), and then treated with pcDNA3.1(+). Animals in treated group (19 mice) and model group (19 mice) were all immunized with splenocytes sensitized by hTSHR, then the former were injected behind the eyeballs with pcDNA3.1(+)/hFasL, while the latter had no special treatment. Results 52.6% in model group 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 treated 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 levels were not statistically significant 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.