Yoshino Osamu, Osuga Yutaka, Koga Kaori, Hirota Yasushi, Hirata Tetsuya, Ruimeng Xie, Na Li, Yano Tetsu, Tsutsumi Osamu, Taketani Yuji
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
J Reprod Immunol. 2006 Dec;72(1-2):85-93. doi: 10.1016/j.jri.2005.02.004. Epub 2006 Aug 4.
In various cells including endometriotic cells, p38 mitogen-activated protein kinase (MAPK) plays essential roles for inflammation, an etiological factor for endometriosis. We evaluated the effect of FR 167653, a p38 MAPK inhibitor, on the development of endometriosis using a murine model. As an endometriosis model, estradiol-treated ovariectomized BALB/c mice were injected intraperitoneally with endometrial fragments of the syngenic donor mice. The animals were injected with either 30mg/kg FR 167653 or only vehicle (control) s.c. twice a day, starting 2 days before endometrial injection. Three weeks later, the peritoneal fluids and the developed endometriotic lesions were collected. Both the weight of all the endometriotic lesions per mouse and the concentrations of interleukin-6 and monocyte chemoattractant protein-1 in the peritoneal fluid were significantly lower in the FR 167653-treated mice than in the control mice. These findings suggest that FR 167653 may inhibit the development of endometriosis possibly by suppressing peritoneal inflammatory status.
在包括子宫内膜异位细胞在内的各种细胞中,p38丝裂原活化蛋白激酶(MAPK)在炎症中发挥着重要作用,而炎症是子宫内膜异位症的一个病因。我们使用小鼠模型评估了p38 MAPK抑制剂FR 167653对子宫内膜异位症发展的影响。作为子宫内膜异位症模型,用雌二醇处理的去卵巢BALB/c小鼠腹腔内注射同基因供体小鼠的子宫内膜碎片。从子宫内膜注射前2天开始,每天两次皮下注射30mg/kg FR 167653或仅注射溶剂(对照)。三周后,收集腹腔液和形成的子宫内膜异位病变。FR 167653处理的小鼠中,每只小鼠所有子宫内膜异位病变的重量以及腹腔液中白细胞介素-6和单核细胞趋化蛋白-1的浓度均显著低于对照小鼠。这些发现表明,FR 167653可能通过抑制腹腔炎症状态来抑制子宫内膜异位症的发展。