Becker Christian M, Wright Renee D, Satchi-Fainaro Ronit, Funakoshi Tae, Folkman Judah, Kung Andrew L, D'Amato Robert J
Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, USA.
Am J Pathol. 2006 Jun;168(6):2074-84. doi: 10.2353/ajpath.2006.051133.
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 full-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 the 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.
子宫内膜异位症是指存在异位子宫内膜组织，是一种常见疾病，伴有高发病率及社会经济问题。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重要作用。我们创建了一种新型的非侵入性模型，用于在体内监测这些病变的生长及相关血管生成。首先，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，我们生成了表达荧光素酶的转基因小鼠。向这些小鼠注射荧光素会引起全身生物发光，可使用低光电荷耦合器件相机进行检测。将这些转基因小鼠的子宫内膜组织手术植入无发光能力的受体体内。在静脉或腹腔注射荧光素后，对病变的生物发光进行非侵入性成像。经腹发光与转基因子宫内膜异位病变的位置吻合良好，且病变大小与发光强度相关。用血管生成抑制剂卡泊他汀和内皮抑素肽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，卡泊他汀使子宫内膜异位病变的生长抑制了59%。这种新型的子宫内膜异位症非侵入性模型为研究体内早期血管生成、监测子宫内膜异位生长及全身抗血管生成治疗的疗效提供了一种手段。
