Department of Obstetrics-Gynecology, The Oncology Institute Prof. Dr. Ion Chiricuta, Cluj-Napoca, Romania.
Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(2):360-5. doi: 10.1016/j.ejogrb.2013.03.022. Epub 2013 Apr 22.
To evaluate the effect of ulipristal on Bax/Bcl-2, cytochrome C, Ki-67 and cyclooxygenase-2 expression in surgically induced endometriosis in a rat model.
We conducted a prospective, randomized, controlled, experimental study at the Experimental Research Center of the Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca, Romania. Endometriosis was induced in 40 female Wistar albino rats by transplanting two autologous fragments of uterine horn onto bowel mesentery. After a 4-week induction period, we formed two groups: the first group was treated with ulipristal (UPA+) for 8 weeks, while the second group was treated only with the vehicle used for ulipristal (UPA-). We measured the volumes and masses of the implants both before and after treatment. A pathologist examined the sections microscopically for histological hallmarks of endometriosis. Immunostaining for Bax/Bcl-2, cytochrome C, Ki-67 and cyclooxygenase-2 (COX-2) was assessed in both groups.
Ulipristal reduced the average implant volume and mass, indicating that the drug is effective (P=0.01). The treatment induced a greater than 50% reduction in the volume and mass of endometrial implants, and the histological findings correspond to this result. The overall Bax positivity rate was higher in the group treated with ulipristal (42.37% vs. 21.05% for UPA+ and UPA-, respectively) (P=0.0062). The overall Bcl-2 positivity rate was smaller in the group treated with ulipristal (15% vs. 40% for UPA+ and UPA-, respectively) (P=0.0593). The cytochrome C global positivity rate was 5% in the UPA- group and increased to 50% in the UPA+ treatment group (P<0.0001). The COX-2 positivity rate decreased from 75% in the UPA- treatment group to 10% in the UPA+ treatment group (P<0.0001) and the Ki67 positivity rate also decreased from 55% in the UPA- group to 10% in the UPA+ treatment group (P<0.0002).
Treatment with ulipristal contributed to the regression and atrophy of endometriotic lesions in rats. The immunohistochemical expression profiles of Bax/Bcl-2 and cytochrome C revealed a pro-apoptotic effect of ulipristal. We also observed a reduced cellular proliferation, indicated by a decrease in Ki-67 expression and an anti-inflammatory effect, shown by a decrease in COX-2 expression after treatment with ulipristal.
评估屈螺酮对大鼠手术诱导子宫内膜异位症模型中 Bax/Bcl-2、细胞色素 C、Ki-67 和环氧化酶-2 表达的影响。
我们在罗马尼亚克卢日-纳波卡的 Iuliu Hatieganu 医科大学实验研究中心进行了一项前瞻性、随机、对照、实验研究。通过将两个自体子宫角片段移植到肠肠系膜上来诱导 40 只雌性 Wistar 白化大鼠的子宫内膜异位症。诱导期 4 周后，我们将其分为两组：第一组用屈螺酮（UPA+）治疗 8 周，而第二组仅用屈螺酮的载体治疗（UPA-）。我们在治疗前后测量了植入物的体积和质量。病理学家对组织学特征进行了镜下检查。我们评估了两组的 Bax/Bcl-2、细胞色素 C、Ki-67 和环氧化酶-2（COX-2）的免疫染色。
屈螺酮降低了平均植入物的体积和质量，表明该药物有效（P=0.01）。治疗使子宫内膜植入物的体积和质量减少了 50%以上，组织学结果与这一结果相符。用屈螺酮治疗的组中整体 Bax 阳性率较高（42.37% vs. UPA+和 UPA-分别为 21.05%）（P=0.0062）。用屈螺酮治疗的组中整体 Bcl-2 阳性率较小（15% vs. UPA+和 UPA-分别为 40%）（P=0.0593）。细胞色素 C 总阳性率在 UPA-组为 5%，在 UPA+治疗组增加到 50%（P<0.0001）。COX-2 阳性率从 UPA-治疗组的 75%下降到 UPA+治疗组的 10%（P<0.0001），Ki67 阳性率也从 UPA-组的 55%下降到 UPA+治疗组的 10%（P<0.0002）。
屈螺酮治疗有助于大鼠子宫内膜异位症病变的消退和萎缩。Bax/Bcl-2 和细胞色素 C 的免疫组织化学表达谱显示屈螺酮具有促凋亡作用。我们还观察到细胞增殖减少，Ki-67 表达下降，COX-2 表达下降，表明屈螺酮治疗具有抗炎作用。
