Soysal D, Kızıldağ S, Saatlı B, Posacı C, Soysal S, Koyuncuoğlu M, Doğan Öe
Dokuz Eylül University, Obstetrics and Gynecology, 35340, İzmir, Turkey.
Dokuz Eylül University, Medical Biology and Genetics, 35340, İzmir, Turkey.
Balkan J Med Genet. 2015 Apr 10;17(2):73-80. doi: 10.2478/bjmg-2014-0077. eCollection 2014 Dec.
Our aim was to investigate the effects of anti-vascular endothelial growth factor (anti-VEGF) antibody Bevacizumab on endometrial explants and on apoptotic gene expression levels in the rat endometriosis model. Endometriotic implants were surgically formed, and rats treated with (i) 1 mg/kg single subcutaneous injection of depot leuprolide acetate; (ii) 2.5 mg/kg of single intaperitoneal injection of bevacizumab; (iii) intraperitoneal injection of saline. Histopathologic scores and adhesion scores of endometriotic foci and levels of Bcl-2-associated X protein (Bax), Cytochrome c (Cyt-c), B-cell lymphoma/leukemia 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) mRNA gene expressions of endometriotic foci. Bevacizumab treatment decreased the endometriotic explant size compared with control. Bevacizumab-treated rats had lower total adhesion scores when compared with the control group. Semi-quantitative evaluation of the persistence of endometrial epithelial cells in the explants showed a lower score in gonadotropin-releasing hormone (GnRH) agonist-treated rats compared with control rats. In Bevacizumab increased expression of Bax 3.1-fold, Cyt-c 1.3-fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold compared with the control group. The GnRH agonist increased expression of Bax 3.0 fold, Cyt-c 1.3 fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold, compared with the control group. This study suggests that a novel angiogenesis inhibitor, anti-VEGF antibody bevacizumab is as effective as GnRH agonist in the regression of the endometriotic lesions in rat endometriosis model. One possible mechanism of this effect is the induction of apoptosis.
我们的目的是研究抗血管内皮生长因子（抗VEGF）抗体贝伐单抗对子宫内膜外植体以及大鼠子宫内膜异位症模型中凋亡基因表达水平的影响。通过手术形成子宫内膜异位植入物，将大鼠分为三组进行治疗：（i）皮下单次注射1mg/kg长效醋酸亮丙瑞林；（ii）腹腔单次注射2.5mg/kg贝伐单抗；（iii）腹腔注射生理盐水。观察子宫内膜异位病灶的组织病理学评分和粘连评分，以及子宫内膜异位病灶中Bcl-2相关X蛋白（Bax）、细胞色素c（Cyt-c）、B细胞淋巴瘤/白血病2（Bcl-2）和B细胞淋巴瘤-特大（Bcl-xl）mRNA基因表达水平。与对照组相比，贝伐单抗治疗可减小子宫内膜异位外植体的大小。与对照组相比，接受贝伐单抗治疗的大鼠总粘连评分更低。对外植体中子宫内膜上皮细胞持久性的半定量评估显示，与对照大鼠相比，促性腺激素释放激素（GnRH）激动剂治疗的大鼠评分更低。与对照组相比，贝伐单抗使Bax表达增加3.1倍，Cyt-c表达增加1.3倍，Bcl-2表达降低0.4倍，Bcl-xl表达降低0.8倍。与对照组相比，GnRH激动剂使Bax表达增加3.0倍，Cyt-c表达增加1.3倍，Bcl-2表达降低0.4倍，Bcl-xl表达降低0.8倍。本研究表明，一种新型血管生成抑制剂——抗VEGF抗体贝伐单抗在大鼠子宫内膜异位症模型中对子宫内膜异位病灶消退的效果与GnRH激动剂相同。这种作用的一种可能机制是诱导细胞凋亡。
