덱사메타손 투여 흰쥐에서 저용량 RhTGF-β1의 창상치유장애 개선효과
Low Dose Treatment of RhTGF-β1 Restore the Wound Healing Defect in Dexamethasone-treated Rats
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전환성장인자-β1 (transforming growth factor-β1, TGF-β1)은 단핵구, 대식세포, 섬유모세포에 대한 화학주성효과와 성장인자 분비 촉진, 교원섬유합성 촉진 등의 작용을 나타냄으로써 창상치유과정에서 매우 중요한조절인자로 작용한다. 본 실험에서는 지속적으로 덱사메타손(dexamethasone)을 투여한 흰쥐를 이용하여 재조합인형 TGF-β1 (recombinant human TGF-β1, rhTGF-β1)의 국소 투여에 의한 창상치유장애의 개선과 이에 따른TGF-βs의 발현 변화를 관찰하고자 하였다. 실험을 위해 8주령의 흰쥐에 덱사메타손 0.1 mg/kg을 매일 피하주사하였다. 3일째에 전층창상을 만든 직후 실험군에는 rhTGF-β1 50 ng을, 정상대조군과 음성대조군에는 동량의 완충용액을 각각의 창상 인접부위에 진피내주사하였다. 수술 후 1, 3, 5, 7, 15일째에 창상면적을 계측하고 창상조직을 채취하여 분석하였다. 창상의 평균 크기는 rhTGF-β1 투여군에서 음성대조군보다 유의한 수준으로 빠르게 감소되었다. 또한 rhTGF-β1의 투여군에서는 세포침윤, 재상피화, 육아조직형성 등의 전반적인 조직학적 소견과 TGF-β1, 2, 3의 발현 양상도 정상대조군과 유사한 수준으로 개선되었다. 이를 통해 rhTGF-β1은 덱사메타손의 투여에 의한 창상치유장애를 개선시킬 수 있으며, 성장인자들의 발현에 직간접적인 효과를 나타냄을 확인하였다.
Abstract
Transforming growth factor-β1 (TGF-β1) has chemotactic effect to monocytes, macrophages and fibroblasts,and it stimulates those cells to produce growth factors and collagen fibers. Therefore, TGF-β1 plays important roles in the wound healing process. The aim of this study is to evaluate the effects of recombinant human TGF-β1(rhTGF-β1) on the wound healing defect in dexamethasone-treated rats. Dexamethasone (0.1 mg/kg/day) was subcutaneously injected into the eight-week-old Sprague-Dawley rats. At the third day of dexamethasone administration, full thickness wounds were made on the back of the rat. And then,rhTGF-β1 (50 ng/wound) was intradermally injected in the vicinity of the wounds. The wounds of the normal and the negative control groups were provided with vehicle only. At 1, 3, 5, 7 and 15 days after the surgery, the wound sizes were measured and the wound tissues were obtained and analyzed. The mean wound sizes of the rhTGF-β1 injected groups were significantly smaller than those of the negative control groups. Moreover, the histologic findings such as cellular infiltration, re-epithelialization and granulation formation and expression patterns of TGF-βs during the wound healing process were improved by administration of rhTGF-β1. These results support that rhTGF-β1 can restore wound healing defect due to dexamethasone administration.
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