Veiga Gisele Almeida Lima, Miziara Ricardo Henrique, Angrimani Daniel Souza Ramos, Papa Paula Carvalho, Cogliati Bruno, Vannucchi Camila Infantosi
Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
Department of Surgery, Sector of Anatomy, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
Biol Reprod. 2017 Jan 1;96(1):58-69. doi: 10.1095/biolreprod.116.140780.
Cystic endometrial hyperplasia (CEH)-pyometra syndrome is one of the most common diseases of noncastrated female dogs. However, determination of etiological mechanisms and differential diagnosis of CEH-pyometra syndrome are undefined. The aim of this study is to compare immunohistochemically the expression of cyclooxygenase-2 (COX-2) inflammatory mediator, Ki-67 antigen proliferation marker, vascular endothelial growth factor (VEGF-A) angiogenesis mediator and its FLT-1 and KDR receptors, and correlate with Doppler velocimetry of uterine artery and endometrial vascularization in bitches with CEH-pyometra syndrome. Bitches were allocated into CEH-mucometra Group (n = 13), Pyometra Group (n = 11), and Control Group (n = 8). Pyometra Group presented cytoplasmatic staining intensity for COX-2, VEGF-A, and FLT-1 and KDR receptors in luminal epithelium cells significantly higher compared to CEH-mucometra and Control groups. For the glandular epithelium, Pyometra Group had higher immunostaining score for VEGF-A and its receptors (FLT-1 and KDR). Hemodynamic indexes showed negative correlation with VEGF-A and its receptors as well as with COX-2. On the other hand, uterine vascularization score showed positive correlation in relation to immunostaining of COX-2, VEGF-A, and receptors in the endometrium luminal epithelium. In conclusion, uterus of bitches with CEH-pyometra syndrome show inflammatory process characterized by COX-2 expression, resulting in greater expression of proliferative Ki-67 marker as tissue response against the infectious agent. Furthermore, the increased VEGF-A expression and its receptors in CEH-pyometra reflect the increased blood flow and lower vascular resistance. Therefore, canine pyometra is characterized by an inflammatory, proliferative, and vascular disorder.
囊性子宫内膜增生（CEH）-积脓综合征是未绝育母犬最常见的疾病之一。然而，CEH-积脓综合征的病因机制及鉴别诊断尚不明确。本研究旨在通过免疫组化比较环氧合酶-2（COX-2）炎症介质、Ki-67抗原增殖标志物、血管内皮生长因子（VEGF-A）血管生成介质及其FLT-1和KDR受体的表达，并与患有CEH-积脓综合征母犬的子宫动脉多普勒测速及子宫内膜血管形成情况相关联。母犬被分为CEH-黏液性子宫积脓组（n = 13）、积脓组（n = 11）和对照组（n = 8）。与CEH-黏液性子宫积脓组和对照组相比，积脓组管腔上皮细胞中COX-2、VEGF-A以及FLT-1和KDR受体的细胞质染色强度显著更高。对于腺上皮，积脓组VEGF-A及其受体（FLT-1和KDR）的免疫染色评分更高。血流动力学指标与VEGF-A及其受体以及COX-2呈负相关。另一方面，子宫血管形成评分与子宫内膜管腔上皮中COX-2、VEGF-A及其受体的免疫染色呈正相关。总之，患有CEH-积脓综合征的母犬子宫表现出以COX-2表达为特征的炎症过程，导致增殖性Ki-67标志物表达增加，作为组织对感染因子的反应。此外，CEH-积脓中VEGF-A及其受体表达增加反映了血流量增加和血管阻力降低。因此，犬积脓的特征为炎症、增殖和血管紊乱。
