Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
Fertil Steril. 2013 Nov;100(5):1459-67. doi: 10.1016/j.fertnstert.2013.07.1967. Epub 2013 Aug 28.
To study the effect of combretastatin A4 phosphate (CA4P) on the vascularization of endometriotic lesions.
Intravital microscopic, histologic, and immunohistochemical study.
University institute.
ANIMAL(S): BALB/c mice.
INTERVENTION(S): Murine endometriotic lesions were induced by syngeneic transplantation of endometrium into dorsal skinfold chambers. After 6 days, the mice received an intraperitoneal injection of 80 mg/kg CA4P or vehicle.
MAIN OUTCOME MEASURE(S): Vascularization of the lesions and the surrounding tissue was analyzed by intravital fluorescence microscopy over 8 days. Lesion morphology, vessel maturation, viability, and proliferation of endometrial glands and stroma were assessed by histology and immunohistochemistry.
RESULT(S): All lesions were initially well vascularized, containing immature and mature microvessels. Injection of CA4P induced a selective vessel collapse in the lesions without affecting the surrounding microvasculature. This resulted in a decreased functional capillary density and blood perfusion of CA4P-treated lesions after 2 hours when compared with controls. However, the vascularization of the lesions progressively normalized, and their numbers of proliferating and apoptotic cells did not differ from those of controls.
CONCLUSION(S): This study demonstrates a selective vascular disrupting effect of CA4P on endometriotic lesions, indicating that vascular disrupting agents may be suitable for endometriosis therapy.
研究 combretastatin A4 磷酸盐(CA4P)对子宫内膜异位病变血管生成的影响。
活体显微镜、组织学和免疫组织化学研究。
大学研究所。
BALB/c 小鼠。
通过将子宫内膜同种异体移植到背部皮褶室中来诱导小鼠子宫内膜异位病变。6 天后,小鼠接受 80mg/kg CA4P 或载体的腹腔内注射。
通过活体荧光显微镜在 8 天内分析病变及其周围组织的血管生成。通过组织学和免疫组织化学评估病变形态、血管成熟度、活力以及子宫内膜腺体和基质的增殖。
所有病变最初均具有良好的血管生成,包含未成熟和成熟的微血管。CA4P 的注射诱导了病变中的选择性血管塌陷,而不影响周围的微血管。与对照组相比,这导致 CA4P 处理的病变中的功能毛细血管密度和血液灌注在 2 小时后降低。然而,病变的血管化逐渐恢复正常,其增殖和凋亡细胞的数量与对照组无差异。
本研究证明了 CA4P 对子宫内膜异位病变的选择性血管破坏作用,表明血管破坏剂可能适用于子宫内膜异位症的治疗。