Carrarelli Patrizia, Funghi Lucia, Bruni Simone, Luisi Stefano, Arcuri Felice, Petraglia Felice
a Division of Obstetrics and Gynecology , Department of Molecular and Developmental Medicine, University of Siena , Siena , Italy.
Gynecol Endocrinol. 2016;32(4):319-22. doi: 10.3109/09513590.2015.1115973. Epub 2015 Dec 3.
Dysmenorrhea, defined as painful cramps occurring immediately before or during the menstrual period, is a common symptom of different gynecological diseases. An acute uterine inflammatory response driven by prostaglandins (PGs) is responsible for painful symptoms. Progesterone withdrawal is responsible for activation of cyclooxygenase (COX-2) enzyme and decrease of hydroxyprostaglandin dehydrogenase (HPDG) with consequent increased secretion of PGs secretion, inducing uterine contractility and pain. The most widely used drugs for the treatment of pelvic pain associated with menstrual cycle are non steroidal anti-inflammatory drugs (NSAIDs). The uterine site of action of these drugs is still not defined and the present study evaluated the effect of naproxen sodium in cultured human endometrial stromal cells (HESC) collected from healthy women. PGE2 release was measured by ELISA; COX-2 and HPDG mRNA expression were assessed by qRT-PCR. Naproxen sodium did not affect HESC vitality. Naproxen sodium significantly decreased PGE2 secretion (p < 0.01) and COX-2 mRNA expression (p < 0.01). TNF-α induced PGE2 release was reduced in presence of naproxen sodium (p < 0.05), in association with decreased COX-2 and increased HPDG mRNAs expression. Naproxen sodium decreases endometrial PGE2 release induced by inflammatory stimulus acting on endometrial COX-2 and HPDG expression, suggesting endometrial synthesis of prostaglandins as a possible target for reduction of uterine inflammatory mechanism in dysmenorrhea.
痛经被定义为在月经前或月经期间立即出现的疼痛性痉挛，是不同妇科疾病的常见症状。由前列腺素（PGs）驱动的急性子宫炎症反应是疼痛症状的原因。孕酮撤退导致环氧化酶（COX - 2）激活和羟前列腺素脱氢酶（HPDG）减少，从而导致PGs分泌增加，诱发子宫收缩和疼痛。治疗与月经周期相关的盆腔疼痛最常用的药物是非甾体抗炎药（NSAIDs）。这些药物在子宫的作用部位仍未明确，本研究评估了萘普生钠对从健康女性收集的培养人子宫内膜基质细胞（HESC）的影响。通过ELISA测量PGE2释放；通过qRT - PCR评估COX - 2和HPDG mRNA表达。萘普生钠不影响HESC活力。萘普生钠显著降低PGE2分泌（p < 0.01）和COX - 2 mRNA表达（p < 0.01）。在萘普生钠存在的情况下，TNF - α诱导的PGE2释放减少（p < 0.05），同时COX - 2表达降低，HPDG mRNA表达增加。萘普生钠通过作用于子宫内膜COX - 2和HPDG表达来减少炎症刺激诱导的子宫内膜PGE2释放，提示前列腺素的子宫内膜合成可能是减轻痛经子宫炎症机制的一个靶点。
