Kacan T, Yildiz C, Baloglu Kacan S, Seker M, Ozer H, Cetin A
Department of Medical Oncology, Cumhuriyet University School of Medicine, Sivas, Turkey.
Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, Sivas, Turkey.
Geburtshilfe Frauenheilkd. 2017 Jan;77(1):66-72. doi: 10.1055/s-0042-115566.
Mammalian target of rapamycin is a pathway to block apoptosis. Recent studies showed that the activity of mammalian target of rapamycin pathway increases in endometriotic lesions. Aim of the present study was to study the effect of everolimus agent, a rapamycin analog, in an experimental endometriosis model. Endometriosis established by the autotransplantation of uterine tissue in the peritoneal cavity was confirmed in 24 rats. The animals were then randomly divided into three groups to receive either everolimus (1.5 mg/kg/day, p. o.), anastrozole (0.004 mg/day, p. o.), or normal saline (0.1 mL, i. p.) for 14 days. Endometriotic foci were excised, stained with hematoxylin and eosin, and endometriosis was scored semiquantitatively. In addition, immunohistochemical examination were performed using primary antibodies of vascular endothelial growth factor, CD117, and Bax. Both anastrozole and everolimus lowered endometriosis scores. Significant decreases in ovarian follicles were observed following anastrozole treatment but not everolimus treatment. Through its apoptosis-promoting effect, everolimus suppressed endometriotic foci without negatively affecting ovarian reserve. These findings support the hypothesis that everolimus merits further study on the way to developing a new endometriosis drug.
雷帕霉素的哺乳动物靶点是一条阻止细胞凋亡的信号通路。最近的研究表明，雷帕霉素靶点信号通路在子宫内膜异位症病灶中的活性增加。本研究的目的是在实验性子宫内膜异位症模型中研究雷帕霉素类似物依维莫司的作用。通过将子宫组织自体移植到腹腔建立子宫内膜异位症模型的24只大鼠得到确认。然后将动物随机分为三组，分别接受依维莫司（1.5毫克/千克/天，口服）、阿那曲唑（0.004毫克/天，口服）或生理盐水（0.1毫升，腹腔注射），持续14天。切除子宫内膜异位病灶，用苏木精和伊红染色，并对子宫内膜异位症进行半定量评分。此外，使用血管内皮生长因子、CD117和Bax的一抗进行免疫组化检查。阿那曲唑和依维莫司均降低了子宫内膜异位症评分。阿那曲唑治疗后观察到卵巢卵泡显著减少，但依维莫司治疗后未观察到。依维莫司通过其促凋亡作用抑制子宫内膜异位病灶，而不会对卵巢储备产生负面影响。这些发现支持了依维莫司值得在开发新的子宫内膜异位症药物方面进一步研究的假设。
