山梨医科大学紀要　第19巻，009-015(2002)

ステロイド治療による創傷治癒障害:
メカニズムの解明と治療法の展望

高野　邦夫，腰塚　浩三，武藤　俊治，毛利　成昭，荒井　洋志，大矢知　昇，
蓮田　憲夫，長阪　智，宮原　和弘，芹沢　大，多田　祐輔

キーワード: 創傷治癒,サイトカイン, ステロイド,成長ホルモン



Mechanism of Adverse Effects of Longterm Corticosteriod
Administration on Wound Healing; Changes of Cytokine Levels and
Effect of Growth Hormone Treatment

TAKANO Kunio, KOSHITUKA Kozo, MUTO Shunji, MOURI Naruaki,
ARAI Hiroshi, OYACHI Noboru, HASUDA Norio, NAGASAKA Satoshi,
MIYAHARA Kazuhiro, SERIZAWA Masaru and TADA Yusuke

The purpose of our study is to clarify the mechanism of the adverse effects of administration of cortico steroids and the effects of human growth hormone （GH） in improving the wounds weakened by long term corticosteroid （CS） administration.
　　Methods: I （epitherisation） ; Sprague-Dawley （SD） male rats were divided into four groups: group （G） 1 ; control, G2 ; covered with film dressing, G3; CS administration （dose, 2 mg/kg/d subcutaneously for 3 weeks preoperatively and throughout the postoperative）. G4 ; CS administration and using film dressing In all animals, the operation consisted of making a circular skin defect of 3 cm diameter, which was covered with a film dressing. Time to 50% wound healing was recorded. II （epitherisation） ; Sprague-Dawley （SD） male rats were divided into four groups: group （G） 1 ; control, G2 ; CS administration （same dose as described） and G3 ; GH treatment （somatotropin, 1 IU/d postoperatively）. G4 ; CS administration animals and GH treatment. In all animals, the operation consisted of making a circular skin defect of 3 cm diameter, which was covered with a film dressing. Time to 50% wound healing was recorded. III （remodeling） ; SD female rats were divide into four groups same as I. All animals underwent a precise 4 cm midline celioyomy which was closed using interrupted 4-0 monofilament nylon sutures. Wound bursting strength （WBS） was tested on postoperative day 6. Histology of wound and liver were evaluated. Cytokine concentrations in both wound exudate and serum were measured.
　　Results: I; The times to 50% wound healing of G1, 3 and 4 were significantly shorter than G2. II; The times to 50% wound healing of G1, 3 and 4 were significantly shorter than G2. Interleukin （IL） -4 and IL-6 concentrations in the exudate of G2 were higher than those of other groups. III; The WBS's of G1, 3 and 4 were significantly greater than those of G2. Serum concentrations of TNF-β, INF-γ, IL-1β & IL-8 of G2 were higher than those of other groups. Conclusion: 1. CS administration not only impairs wound healing but also causes hypercytokinemia. In animals of CS administration. 2. Postoperative systemic GH restores the strength of wound and cytokine levels.

KEY WORDS : WOUND HEALING, CYTOKINE, CORTICOSTEROID, GROWTH HORMONE


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