The effects of cyclooxygenase isozyme inhibition on incisional wound healing in mouse skin.

The effects of cyclooxygenase isozyme inhibition on incisional wound healing in mouse skin.
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环氧合酶同工酶抑制对小鼠皮肤切口伤口愈合的影响。

DOI:
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发表时间:
2002
影响因子:
6.5
通讯作者:
G. Fürstenberger
G. Fürstenberger
中科院分区:
医学1区
文献类型:
--
作者:
K. Müller;W. Hirschner;F. Marks;G. Fürstenberger

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前列腺素除了具有促炎活性外,最近还被证明有助于组织损伤和炎症的消退。因此,抑制环氧合酶-2,在这些条件下的主要前列腺素内过氧化合成酶,可能不仅导致炎症反应减弱,而且还延缓了组织的再生和修复。为此,我们研究了环氧合酶同工酶的表达以及环氧合酶抑制剂对小鼠皮肤全层伤口愈合的影响。免疫组织化学分析显示,环氧合酶同工酶在增生性上皮角质形成细胞中有显著表达,环氧合酶-1免疫信号主要分布在基底室,环氧合酶-2免疫信号遍及整个表皮。此外,类似朗格汉斯细胞的树突状细胞以及肉芽组织附近或肉芽组织内的内皮细胞和巨噬细胞都表达这两种同工酶。口服环氧合酶-1选择性抑制剂SC-560或环氧合酶-2选择性抑制剂valdecoxib抑制前列腺素E_2的合成,从宏观上看并没有延缓小鼠皮肤伤口的愈合。除了创伤诱导新生血管形成后早期上皮化有轻微的暂时性延迟外,这些药物并没有延迟胶原沉积和抗张强度的恢复。同样,非选择性抑制剂吲哚美辛对伤口的抗张强度没有影响。
In addition to their proinflammatory activities, prostaglandins recently have been shown to be beneficial in the resolution of tissue injury and inflammation. Thus, inhibition of cyclooxygenase-2, the predominant prostaglandin endoperoxide synthase under these conditions, may not only result in attenuating the inflammatory response but also in delaying tissue regeneration and repair. To this end, we investigated cyclooxygenase isozyme expression and the effects of cyclooxygenase inhibitors on wound healing upon full-thickness incisions in mouse skin. Immunohistochemical analysis revealed prominent expression of cyclooxygenase isozymes in keratinocytes of the hyperplastic epithelium, with cyclooxygenase-1 immunosignals predominating in the suprabasal compartment and cyclooxygenase-2 immunosignals spread throughout the whole epidermis. Moreover, dendritic cells, resembling Langerhans cells, as well as endothelial cells and macrophages in the vicinity of or within the granulation tissue were found to express both isozymes. Inhibition of prostaglandin E2 synthesis by oral administration of the cyclooxygenase-1-selective inhibitor SC-560 or the cyclooxygenase-2-selective inhibitor valdecoxib did not retard wound healing in mouse skin macroscopically. Except for a slight transient retardation of epithelialization early after wounding wound-induced neoangiogenesis, collagen deposition, and the restoration of tensile strength were not delayed by these agents. Likewise, the nonselective inhibitor indomethacin had no effect on the tensile strength of incisional skin wounds.
DOI: --
发表时间: 2000-01
期刊: Cancer research
影响因子: 11.2
作者:
B. Reddy;Y. Hirose;R. Lubet;V. Steele;G. Kelloff;Susan Paulson;Karen Seibert;C. Rao
通讯作者: B. Reddy;Y. Hirose;R. Lubet;V. Steele;G. Kelloff;Susan Paulson;Karen Seibert;C. Rao
DOI: 10.1016/s0016-5085(98)70259-8
发表时间: 1998-10-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
作者:
Tessner, TG;Cohn, SM;Stenson, WF
通讯作者: Stenson, WF