Kelley S F, Felix A M, Ehrlich H P
Shriners Burns Institute, Massachusetts General Hospital, Boston 02114.
Proc Soc Exp Biol Med. 1990 Sep;194(4):320-6. doi: 10.3181/00379727-194-43098.
Daily therapeutic injections of cortisone to rats will cause weight loss and impaired wound healing. Weight loss is attributed to the catabolic effect of steroid, whereas impaired healing is associated with reductions in fibroplasia and connective tissue deposition. As the major structural protein component of connective tissue is collagen, its absence is responsible for the retarded gain in wound breaking strength. Cortisone also blocks wound closure by inhibiting wound contraction. An anabolic agent such as growth hormone may antagonize the effect of cortisone on the wound healing process. Endogenous GH can be released from the pituitary by exogenous injections of growth hormone-releasing factor (GRF). Two synthetic GRF peptides, a natural 44-amino acid peptide of the human GRF sequence, GRF-44, and an N-terminally substituted analog 29 residues, GRF-29A, were studied. Each was given twice daily with a single daily injection of cortisone for a 7-day period. Concurrent administration of GRF-44 or GRF-29A and cortisone to rats had no effect on restored body weight loss or inhibited wound contraction. While GRF-44 restored collagen deposition and caused restored wound breaking strength, GRF-29A was ineffective in restoring either. GRF-44, a synthetic peptide that stimulates pituitary release of growth hormone, antagonized some of the inhibiting effect of steroid on wound repair by promoting fibroplasia and collagen deposition.
每日给大鼠注射可的松会导致体重减轻和伤口愈合受损。体重减轻归因于类固醇的分解代谢作用，而愈合受损则与纤维增生和结缔组织沉积减少有关。由于结缔组织的主要结构蛋白成分是胶原蛋白，其缺乏导致伤口抗张强度增加延迟。可的松还通过抑制伤口收缩来阻碍伤口闭合。一种合成代谢剂，如生长激素，可能会拮抗可的松对伤口愈合过程的影响。通过外源性注射生长激素释放因子（GRF）可使内源性生长激素从垂体释放。研究了两种合成GRF肽，一种是具有人类GRF序列的天然44个氨基酸的肽，GRF - 44，以及一种N端取代的29个残基的类似物，GRF - 29A。在为期7天的时间里，每种肽每天给药两次，并每日单次注射可的松。同时给大鼠注射GRF - 44或GRF - 29A与可的松，对恢复体重减轻或抑制伤口收缩均无影响。虽然GRF - 44恢复了胶原蛋白沉积并使伤口抗张强度恢复，但GRF - 29A在恢复这两者方面均无效。GRF - 44是一种刺激垂体释放生长激素的合成肽，通过促进纤维增生和胶原蛋白沉积，拮抗了类固醇对伤口修复的一些抑制作用。
