机体保护多肽BPC-157促进烧伤创面愈合的关键分子鉴定

Burns is a very complicated traumatic disease which is caused by physical, chemical, radiation and many other factors affecting on the body. The treatment of burn wound healing is still a big problem, so searching, detecting and identifying related molecules involving in burn wound healing, and clarifying mechanism underlying is of great significance. The body protection compound 157 (BPC-157) is a composed of 15 amino acid polypeptide. Our previous studies have found that the BPC-157 has good promoting burn wound healing effect and can significantly enhance proliferation, migration and tube formation of endothelial cell. These results suggest that BPC-157 can be a candidate for therapeutic agents in the treatment of burn wound healing. However, the specific molecular mechanism is unclear. Based on previous data, we plan to take the studies of BPC-157 interaction partners as a breakthrough, utilize affinity purification, tandem mass spectrometry, RNAi, gene transfection, and immunofluorescence to screen the BPC-157 binding-partners, study its influence on endothelial cells and preliminary to elucidate the role of the interaction in burn wound healing process. This study is to put forward a new understanding for repair mechanism of burned skin, and to provide the basis for elucidating the BPC-157 drug targets of promoting wound healing.

烧伤是物理、化学、放射等诸多因素作用于机体所造成的一种极其复杂的外伤性疾病，创面愈合仍是烧伤治疗中的一大难题，寻找、发现和鉴定参与烧伤创面愈合的相关分子，并阐明其作用机制意义重大。BPC-157是一个由15个氨基酸组成的多肽，本课题组前期研究发现BPC-157具有良好的促进烧伤创面愈合的作用，可显著增强内皮细胞的增殖、迁移及小管形成等生物学功能。上述结果提示，BPC-157可考虑作为治疗烧伤创面愈合的候选药物，但其与靶细胞作用的首触分子尚不清楚。本课题拟在前期工作基础上，以探明BPC-157的相互作用分子为突破口，综合利用亲和纯化、串联质谱、RNAi、基因转染和免疫荧光等实验技术，系统研究能够与BPC-157相互作用的分子及其对内皮细胞的影响，初步阐明这种相互作用在烧伤创面愈合过程中的作用，该研究既为烧伤皮肤修复机理提出新认识，又为阐明BPC-157促进创面愈合的药物作用靶点提供依据。

创面愈合是各类表皮损伤中的关键过程，寻找、发现能够加速创面愈合、降低感染发生的有效途径是治疗创面愈合的核心。BPC-157是一个由15个氨基酸组成的多肽，本课题组前期研究发现BPC-157具有良好的促进烧伤创面愈合的作用，可显著增强内皮细胞的增殖、迁移及小管形成等生物学功能。上述结果提示，BPC-157可考虑作为治疗创面愈合的候选药物。我们进一步研究发现：① BPC-157可促进皮肤伤口愈合；② BPC-157可通过增加肉芽组织胶原沉积、提高肉芽组织羟脯氨酸水平、组织DNA含量等途径促进创面损伤愈合；③ BPC-157治疗改变了皮肤胶原沉积，促进皮肤损伤修复；④ 大鼠、小鼠、比格犬BPC-157重复给药的安全性良好，未见显著不良反应；⑤ BPC-157局部给药耐受良好，对皮肤无明显致敏性；⑥ 治疗剂量范围内BPC-157无体外遗传毒性和胚胎毒性。以上研究结果不仅有助于深入理解BPC-157的功能，为创面愈合治疗提供新的备选药物，同时为全面开展BPC-157临床试验奠定基础。