Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
Angiogenesis. 2013 Jan;16(1):59-69. doi: 10.1007/s10456-012-9299-4. Epub 2012 Sep 5.
Green tea epigallocatechin-3-gallate (EGCG) can inhibit angiogenesis and development of an experimental endometriosis model in mice, but it suffers from poor bioavailability. A prodrug of EGCG (pro-EGCG, EGCG octaacetate) is utilized to enhance the stability and bioavailability of EGCG in vivo. In this study, the potential of pro-EGCG as a potent anti-angiogenesis agent for endometriosis in mice was investigated. Homologous endometrium was subcutaneously transplanted into mice to receive either saline, vitamin E, EGCG or pro-EGCG treatment for 4 weeks. The growth of the endometrial implants were monitored by IVIS(®) non-invasive in vivo imaging during the interventions. Angiogenesis of the endometriotic lesions was determined by Cellvizio(®) in vivo imaging and SCANCO(®) Microfil microtomography. The bioavailability, anti-oxidation and anti-angiogenesis capacities of the treatments were measured in plasma and lesions. The implants with adjacent outer subcutaneous and inner abdominal muscle layers were collected for histological, microvessel and apoptosis examinations. The result showed that EGCG and pro-EGCG significantly decreased the growth of endometrial implants from the 2nd week to the 4th week of intervention. EGCG and pro-EGCG significantly reduced the lesion size and weight, inhibited functional and structural microvessels in the lesions, and enhanced lesion apoptosis at the end of interventions. The inhibition by pro-EGCG in all the angiogenesis parameters was significantly greater than that by EGCG, and pro-EGCG also had better bioavailability and greater anti-oxidation and anti-angiogenesis capacities than EGCG. Ovarian follicles and uterine endometrial glands were not affected by either EGCG or pro-EGCG. Vitamin E had no effect on endometriosis. In conclusion, pro-EGCG significantly inhibited the development, growth and angiogenesis of experimental endometriosis in mice with high efficacy, bioavailability, anti-oxidation and anti-angiogenesis capacities. Pro-EGCG could be a potent anti-angiogenesis agent for endometriosis.
绿茶表没食子儿茶素-3-没食子酸酯（EGCG）可抑制小鼠实验性子宫内膜异位症模型的血管生成和发展，但它的生物利用度较差。EGCG 的前药（前 EGCG，EGCG 辛二酸酯）用于提高 EGCG 在体内的稳定性和生物利用度。在这项研究中，研究了前 EGCG 作为一种潜在的抗血管生成药物治疗小鼠子宫内膜异位症的潜力。同源子宫内膜被皮下移植到小鼠体内，分别接受生理盐水、维生素 E、EGCG 或前 EGCG 治疗 4 周。在干预过程中，通过 IVIS（®）非侵入性体内成像监测子宫内膜植入物的生长。通过 Cellvizio（®）体内成像和 SCANCO（®）Microfil 微断层扫描确定子宫内膜异位症病变的血管生成。测量血浆和病变中的治疗物的生物利用度、抗氧化和抗血管生成能力。收集带有相邻的皮下外层和腹部内层肌肉层的植入物进行组织学、微血管和细胞凋亡检查。结果表明，EGCG 和前 EGCG 从干预的第 2 周到第 4 周显著降低了子宫内膜植入物的生长。EGCG 和前 EGCG 显著减小了病变的大小和重量，抑制了病变中的功能性和结构性微血管，并在干预结束时增强了病变的细胞凋亡。前 EGCG 在所有血管生成参数中的抑制作用明显大于 EGCG，前 EGCG 的生物利用度更高，抗氧化和抗血管生成能力也更强。EGCG 和前 EGCG 对卵巢卵泡和子宫子宫内膜腺体均无影响。维生素 E 对子宫内膜异位症没有影响。总之，前 EGCG 以高效、生物利用度、抗氧化和抗血管生成能力显著抑制了实验性子宫内膜异位症在小鼠中的发展、生长和血管生成。前 EGCG 可能是一种有效的抗血管生成药物治疗子宫内膜异位症。
