Department of Gynecology, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium.
Hum Reprod. 2010 Mar;25(3):734-41. doi: 10.1093/humrep/dep408. Epub 2009 Dec 19.
Increased peritoneal eicosanoid concentrations have been reported in endometriosis patients and might be important in disease-associated pain and inflammation. Here, we evaluated the expression of key biosynthetic and catabolic enzymes involved in this abnormal eicosanoid production in peritoneal macrophages and endometriotic lesions.
Peritoneal macrophages, endometriotic lesions and matched eutopic endometrium were collected from endometriosis patients (n = 40). Peritoneal macrophages and eutopic endometrium samples were also collected from disease-free women (n = 25). Expression of type IIA secretory phospholipase A(2) (sPLA(2)-IIA), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 5-lipoxygenase (5-LO) was quantified by real-time PCR, and these five key enzymes were localized by immunohistochemistry.
sPLA(2)-IIA, COX-2 and mPGES-1 mRNA was significantly increased in peritoneal macrophages of endometriosis patients compared with controls (P = 0.006, P = 0.016 and P = 0.025, respectively). In endometriosis patients, sPLA(2)-IIA, mPGES-1 and 15-PGDH mRNA was significantly enhanced in peritoneal lesions compared with matched eutopic endometrium (P < 0.001, P < 0.001 and P = 0.005, respectively). In eutopic endometrium, a significant decrease in 15-PGDH mRNA was found in the endometriosis group compared with controls (P = 0.023). Finally, sPLA(2)-IIA, COX-2, mPGES-1 and 15-PGDH immunostaining was found mainly in endometrial glands, whereas 5-LO was distributed throughout the glands and stroma.
Our study highlights an imbalance between eicosanoid biosynthesis and degradation in endometriosis patients. Both peritoneal macrophages and endometriotic lesions may be involved. Research into new molecules inhibiting biosynthetic enzymes (such as sPLA(2)-IIA and mPGES-1) and/or activating catabolic enzymes (such as 15-PGDH) may prove to be a major field of investigation in the development of targeted medical therapies.
已报道子宫内膜异位症患者的腹腔内花生四烯酸浓度增加，这可能与疾病相关的疼痛和炎症有关。在此，我们评估了参与腹腔巨噬细胞和子宫内膜异位症病变中异常花生四烯酸产生的关键生物合成和分解代谢酶的表达。
从子宫内膜异位症患者（n=40）中收集腹腔巨噬细胞、子宫内膜异位症病变和匹配的在位子宫内膜。还从无疾病的女性（n=25）中收集腹腔巨噬细胞和在位子宫内膜样本。通过实时 PCR 定量测定 IIA 型分泌型磷脂酶 A2（sPLA2-IIA）、环氧化酶-2（COX-2）、微粒体前列腺素 E 合酶-1（mPGES-1）、15-羟基前列腺素脱氢酶（15-PGDH）和 5-脂氧合酶（5-LO）的表达，并通过免疫组织化学定位这五种关键酶。
与对照组相比，子宫内膜异位症患者的腹腔巨噬细胞中 sPLA2-IIA、COX-2 和 mPGES-1 mRNA 显著增加（P=0.006、P=0.016 和 P=0.025）。在子宫内膜异位症患者中，与匹配的在位子宫内膜相比，腹腔病变中 sPLA2-IIA、mPGES-1 和 15-PGDH mRNA 显著增强（P<0.001、P<0.001 和 P=0.005）。在在位子宫内膜中，与对照组相比，子宫内膜异位症组中 15-PGDH mRNA 显著降低（P=0.023）。最后，sPLA2-IIA、COX-2、mPGES-1 和 15-PGDH 免疫染色主要在子宫内膜腺体中发现，而 5-LO 分布在腺体和基质中。
我们的研究强调了子宫内膜异位症患者中花生四烯酸生物合成和降解之间的不平衡。腹腔巨噬细胞和子宫内膜异位症病变都可能参与其中。研究新的抑制生物合成酶（如 sPLA2-IIA 和 mPGES-1）和/或激活分解代谢酶（如 15-PGDH）的分子可能成为开发靶向治疗药物的主要研究领域。
Zotero 插件