Carney D H, Mann R, Redin W R, Pernia S D, Berry D, Heggers J P, Hayward P G, Robson M C, Christie J, Annable C
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
J Clin Invest. 1992 May;89(5):1469-77. doi: 10.1172/JCI115737.
To better define thrombin-receptor interactions, we synthesized human thrombin peptides and identified binding-domain peptides that bind thrombin receptors and activate mitogenic signals (Glenn, K.C., G.H. Frost, J.S. Bergmann, and D.H. Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with a single topical application of thrombin receptor-activating peptide (TRAP-508) or human alpha-thrombin in saline enhances 7-d incisional breaking strength in normal rats up to 82% or 55% over saline-treated controls, respectively. Control wounds require approximately 11.5 d to achieve breaking strength equivalent to TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates healing, shifting the time course forward by up to 4.5 d. Histological comparisons at day 7 show more type I collagen, less evidence of prolonged inflammation, and an increase in number and maturity of capillaries in TRAP- and thrombin-treated incisions. Angiograms also show 50-65% more functional vascularization going across thrombin- and TRAP-treated surgical incisions. Thus, alpha-thrombin and thrombin peptides, such as those released following injury, appear to initiate or enhance signals required for neovascularization and wound healing. The ability to accelerate normal wound healing events with synthetic peptides representing receptor binding domains of human thrombin may offer new options for management of wound healing in man.
为了更好地定义凝血酶-受体相互作用，我们合成了人凝血酶肽，并鉴定出能结合凝血酶受体并激活促有丝分裂信号的结合域肽（格伦，K.C.，G.H.弗罗斯特，J.S.伯格曼，和D.H.卡尼。1988年。《肽研究》1:65 - 73）。在正常大鼠中，单次局部应用凝血酶受体激活肽（TRAP - 508）或生理盐水溶解的人α - 凝血酶处理全层背部皮肤切口，可使7天切口抗张强度分别比生理盐水处理的对照组提高82%或55%。对照伤口需要约11.5天才能达到与第7天TRAP处理伤口相当的抗张强度。因此，单次应用TRAP可加速愈合，将时间进程提前多达4.5天。第7天的组织学比较显示，TRAP和凝血酶处理的切口中I型胶原蛋白更多，炎症持续的迹象更少，毛细血管数量和成熟度增加。血管造影还显示，穿过凝血酶和TRAP处理的手术切口的功能性血管生成增加50 - 65%。因此，α - 凝血酶和凝血酶肽，如损伤后释放的那些，似乎启动或增强了新血管形成和伤口愈合所需的信号。用代表人凝血酶受体结合域的合成肽加速正常伤口愈合过程的能力，可能为人类伤口愈合的管理提供新的选择。
