Kämpfer Heiko, Bräutigam Lutz, Geisslinger Gerd, Pfeilschifter Josef, Frank Stefan
Pharmazentrum Frankfurt Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
J Invest Dermatol. 2003 May;120(5):880-90. doi: 10.1046/j.1523-1747.2003.12140.x.
This investigation demonstrated a functional coupling between cyclooxygenase-1 (cox) and prostaglandin E2/D2 biosynthesis in murine skin repair. Cyclooxygenase-1 expression decreased transiently after excisional wounding, and this was followed by a marked fall in the rate of prostaglandin E2/D2 biosynthesis at the wound site. Expression of cyclooxygenase-1, prostaglandin synthases, and prostaglandin E2/D2 production were colocalized in new tissue at the margin of the wound. Although cyclooxygenase-2 expression was strongly induced in granulation tissue on injury, this isoform did not contribute to high prostaglandin E2/D2 concentrations in wounds. Accordingly, wound tissue from SC-560-treated mice (selective cyclooxygenase-1 inhibitor) and diclofenac-treated mice (nonselective cyclooxygenase inhibitor), but not celecoxib-treated mice (selective cyclooxygenase-2 inhibitor), and wound tissue from cyclooxygenase-1-deficient animals exhibited a severe loss of prostaglandin E2/D2 at the wound site, and this change was associated with an impairment in the normal wound morphology. Topically administered prostaglandin E2 (dinoprostone) was able to restore normal wound repair to diclofenac-treated mice. In contrast to the presence of an injury-induced cyclooxygenase-2, these data constitute strong evidence that cyclooxygenase-1-coupled prostaglandin E2/D2 biosynthesis has a central role in skin repair.
本研究证明了环氧化酶-1（COX）与前列腺素E2/D2生物合成在小鼠皮肤修复过程中的功能偶联。切除伤口后，环氧化酶-1的表达短暂下降，随后伤口部位前列腺素E2/D2的生物合成速率显著降低。环氧化酶-1、前列腺素合酶的表达以及前列腺素E2/D2的产生在伤口边缘的新组织中共同定位。尽管在损伤后的肉芽组织中环氧化酶-2的表达被强烈诱导，但该同工型对伤口中高浓度的前列腺素E2/D2并无贡献。因此，来自SC-560处理小鼠（选择性环氧化酶-1抑制剂）和双氯芬酸处理小鼠（非选择性环氧化酶抑制剂）的伤口组织，但不包括塞来昔布处理小鼠（选择性环氧化酶-2抑制剂）的伤口组织，以及来自环氧化酶-1缺陷动物的伤口组织，在伤口部位均表现出前列腺素E2/D2的严重缺失，且这种变化与正常伤口形态的受损有关。局部应用前列腺素E2（地诺前列酮）能够使双氯芬酸处理的小鼠恢复正常的伤口修复。与损伤诱导的环氧化酶-2的存在相反，这些数据有力地证明了环氧化酶-1偶联的前列腺素E2/D2生物合成在皮肤修复中起核心作用。
