打开APP

Endocrinology:开发出治疗甲状腺机能亢进的新型动物模型

  1. Endocrinology
  2. 动物模型
  3. 机能亢进
  4. 甲状腺

来源:生物谷 2013-09-03 22:25

2013年9月3日 讯 /生物谷BIOON/ --近日,刊登在国际著名杂志Endocrinology上的一篇研究报道中,来自伦敦国王学院医学院的研究者通过研究开发出了一种新型的动物模型,其可以模拟和甲状腺机能亢进相关的眼部并发症,甲状腺机能亢进(Graves' disease)是一种自体免疫障碍,其可以引发机体产生攻击甲状腺的抗体,从而引发抗体过度激活而产生过多的甲状腺激素...

2013年9月3日 讯 /生物谷BIOON/ --近日,刊登在国际著名杂志Endocrinology上的一篇研究报道中,来自伦敦国王学院医学院的研究者通过研究开发出了一种新型的动物模型,其可以模拟和甲状腺机能亢进相关的眼部并发症,甲状腺机能亢进(Graves' disease)是一种自体免疫障碍,其可以引发机体产生攻击甲状腺的抗体,从而引发抗体过度激活而产生过多的甲状腺激素,如果没有得到及时治疗就会引发患者心衰甚至骨质疏松。

在文中,研究者J. Paul Banga表示,当前治疗和甲状腺机能亢进相关的眼部并发症的疗法非常有限,用于治疗甲状腺机能相关的眼眶病的较好的疗法可以降低永久性毁容的风险;研究者开发出的动物模型可以检测相关的预防疗法是否可以使得患者获益。

尽管在过去研究者已经开发出了一种动物模型,但是当时的动物模型并不能复制而且也不能被刺激产生和甲状腺机能亢进相关的眼部问题。为了开发本文的新型模型,研究者通过将特殊质粒注射入小鼠体内,经过三个月时间,研究者使用电子脉冲来检测确定是否这种质粒分子被小鼠完全吸收。

新开发的动物模型可以产生和甲状腺机能亢进相关的眼部障碍,这就为科学家研究疾病发生的分子机制以及判断一些预防疗法是否有效、以及开发相应的疗法提供帮助和希望。(生物谷Bioon.com)

Cutting Edge: Retrobulbar Inflammation, Adipogenesis, and Acute Orbital Congestion in a Preclinical Female Mouse Model of Graves' Orbitopathy Induced by Thyrotropin Receptor Plasmid-in Vivo Electroporation

Sajad Moshkelgosha, Po-Wah So, Neil Deasy, Salvador Diaz-Cano and J Paul Banga

Graves' orbitopathy (GO) is a complication in Graves' disease (GD) but mechanistic insights into pathogenesis remain unresolved, hampered by lack of animal model. The TSH receptor (TSHR) and perhaps IGF-1 receptor (IGF-1R) are considered relevant antigens. We show that genetic immunization of human TSHR (hTSHR) A-subunit plasmid leads to extensive remodeling of orbital tissue, recapitulating GO. Female BALB/c mice immunized with hTSHR A-subunit or control plasmids by in vivo muscle electroporation were evaluated for orbital remodeling by histopathology and magnetic resonance imaging (MRI). Antibodies to TSHR and IGF-1R were present in animals challenged with hTSHR A-subunit plasmid, with predominantly TSH blocking antibodies and were profoundly hypothyroid. Orbital pathology was characterized by interstitial inflammation of extraocular muscles with CD3+ T cells, F4/80+ macrophages, and mast cells, accompanied by glycosaminoglycan deposition with resultant separation of individual muscle fibers. Some animals showed heterogeneity in orbital pathology with 1) large infiltrate surrounding the optic nerve or 2) extensive adipogenesis with expansion of retrobulbar adipose tissue. A striking finding that underpins the new model were the in vivo MRI scans of mouse orbital region that provided clear and quantifiable evidence of orbital muscle hypertrophy with protrusion (proptosis) of the eye. Additionally, eyelid manifestations of chemosis, including dilated and congested orbital blood vessels, were visually apparent. Immunization with control plasmids failed to show any orbital pathology. Overall, these findings support TSHR as the pathogenic antigen in GO. Development of a new preclinical model will facilitate molecular investigations on GO and evaluation of new therapeutic interventions.

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->