A novel noninvasive model of endometriosis for monitoring the efficacy of antiangiogenic therapy
A novel noninvasive model of endometriosis for monitoring the efficacy of antiangiogenic therapy
复制标题
DOI：
10.2353/ajpath.2006.051133
复制
发表时间：
2006-06-01
影响因子：
6
通讯作者：
D'Amato, Robert J.
中科院分区：
文献类型：
--
作者：
Becker, Christian M.;Wright, Renee D.;D'Amato, Robert J.
子宫内膜异位症是异位子宫内膜组织的存在，是一种与高发病率和社会经济问题相关的常见疾病。血管生成，即新血管的形成，在子宫内膜异位病变的形成和生长中起着重要作用。我们创建了一种新颖的非侵入性模型来监测这些病变的生长以及体内相关的血管生成。首先，我们通过插入与萤火虫荧光素酶报告基因偶联的人泛素 C 启动子来产生表达荧光素酶的转基因小鼠。在这些小鼠体内注射荧光素会引起山体生物发光，可以使用低光 CCD 相机检测到。这些转基因小鼠的子宫内膜组织通过手术植入不发光受体体内。静脉内或腹膜内注射荧光素后，对病变的生物发光进行无创成像。经腹部发光与转基因子宫内膜异位病变的位置进行了很好的比较，并且病变大小与发光强度相关。用血管生成抑制剂卡普他汀和内皮抑素肽mP-1进行全身治疗可延迟并抑制发光信号的出现和强度。与对照组相比，Caplostatin 可抑制子宫内膜异位病变的生长 59%。这种新型的、非侵入性的子宫内膜异位症模型提供了一种研究体内早期血管生成、监测子宫内膜异位症生长和全身抗血管生成治疗疗效的方法。
Endometriosis, the presence of ectopic endometrial tissue, is a common disease associated with high morbidity and socioeconomic problems. Angiogenesis, the formation of new blood vessels, plays an important role in the formation and growth of endometriotic lesions. We have created a novel, noninvasive model to monitor the growth of these lesions and the associated angiogenesis in vivo. First, we generated luciferase-expressing transgenic mice by inserting the human ubiquitin C promoter coupled to the firefly luciferase reporter. Injection of luciferin in these mice causes hill-body bioluminescence, which can be detected using a low-light CCD camera. Endometrial tissue from these transgenic mice was surgically implanted into nonluminescent recipients. Bioluminescence of lesions was noninvasively imaged after intravenous or intraperitoneal injection of luciferin. Transabdominal luminescence compared well with die location of the transgenic endometriotic lesions, and lesion size correlated with the intensity of luminescence. Systemic treatment with the angiogenesis inhibitors caplostatin and endostatin peptide mP-1 delayed and suppressed the onset and intensity of the luminescent signal. Caplostatin suppressed the growth of endometriotic lesions by 59% compared with controls. This novel, noninvasive model of endometriosis provides a means to study early angiogenesis in vivo and to monitor endometriotic growth and the efficacy of systemic antiangiogenic therapy.