Kaitu'u Tu'uhevaha J, Shen Jun, Zhang Jin, Morison Naomi B, Salamonsen Lois A
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Biol Reprod. 2005 Oct;73(4):672-80. doi: 10.1095/biolreprod.105.042473. Epub 2005 Jun 8.
Considerable correlative evidence suggests an important role for matrix metalloproteinases (MMPs) in menstruation, a process which occurs naturally in very few species. In this study, MMP expression was examined in a mouse model of endometrial breakdown and repair and the functional importance of MMPs determined. In the model, progesterone support was withdrawn from mice in which endometrial decidualization had been induced; 24 h later, endometrial breakdown was complete, and the entire decidual zone had been shed. Re-epithelialization had occurred by 36 h, and the endometrium had undergone extensive restoration toward a predecidualized state by 48 h. Immunoreactive MMP9 and MMP7 colocalized with leukocyte subsets, particularly neutrophils, whereas MMP13 staining was always extracellular. MMP3 and MMP7 were abundant during re-epithelialization in close proximity to newly reforming epithelium. The functional importance of MMPs in these processes was examined using two MMP inhibitors, doxycycline and batimistat. Both inhibitors effectively reduced MMP activity, as assessed by in situ zymography, but did not have significant effects on endometrial breakdown or repair. This study demonstrates that although MMPs are present in abundance during endometrial breakdown and repair in this mouse model, they are not the key mediators of these processes.
大量相关证据表明，基质金属蛋白酶（MMPs）在月经过程中发挥重要作用，而月经是极少数物种自然发生的过程。在本研究中，研究人员在子宫内膜崩解和修复的小鼠模型中检测了MMP的表达，并确定了MMPs的功能重要性。在该模型中，对已诱导子宫内膜蜕膜化的小鼠停止给予孕酮支持；24小时后，子宫内膜崩解完成，整个蜕膜区脱落。36小时时发生了重新上皮化，到48小时时，子宫内膜已朝着蜕膜化前状态进行了广泛修复。免疫反应性MMP9和MMP7与白细胞亚群共定位，尤其是中性粒细胞，而MMP13染色始终位于细胞外。MMP3和MMP7在重新上皮化过程中靠近新形成的上皮处大量存在。使用两种MMP抑制剂强力霉素和巴马司他研究了MMPs在这些过程中的功能重要性。通过原位酶谱分析评估，两种抑制剂均有效降低了MMP活性，但对子宫内膜崩解或修复没有显著影响。这项研究表明，尽管在该小鼠模型的子宫内膜崩解和修复过程中MMPs大量存在，但它们不是这些过程的关键介质。
