中文摘要
针对创伤修复与组织再生,基因工程和干细胞技术虽然有效,但也仅能解决部分问题且价格高昂,糖尿病足、各种溃疡等慢性创伤修复仍面临挑战。著名的蚯蚓、壁虎、章鱼、蝾螈的断肢再生及近年兴起的蛆虫疗法均展现出动物对于创面修复的优势。由美洲大蠊(ML)制成的主要由小分子组成的康复新液临床上愈创效果突出,且不留疤痕,但药效物质基础长期不明。前期,我们发现ML的不同组分在不同细胞模型上确有愈创活性,继而从ML中鉴定40余个结构多样的化合物,并发现部分成分具有抗炎、促胶原分泌、调节Wnt/β-catenin等愈创活性,初步揭示了ML愈创有其物质基础。由于HPLC显示ML中成分尤其是高极性成分众多,但它们的结构特征、在炎症反应、肉芽形成及组织重建中的角色及作用特点等均有待阐明。因此本项目围绕上述科学问题深入挖掘,有望充分解析ML愈创物质基础,绘制成分/效应网络,支撑康复新液临床应用,并为开发愈创药物提供新视角。
英文摘要
Wound healing and tissue regeneration is implicated in a wide range of disorders. Although stem cell therapy and genetic engineering technology displays advantages and accounts for advanced therapy in this field, it is still a great challenge for chronic wound repair exemplified as diabetic foot and various chronic ulcers. Therefore, it is urgently necessary to make efforts on improving therapeutic approaches of chronic wound repair. In nature, some animals such as earthworms, geckoes, octopuses, and salamanders are unique in showing the high capacity for regeneration, including full limb and tail regeneration. Besides ancient maggot therapy receives great attentions nowadays due to its magic efficacy in wound repair. All these examples demonstrate that animals or animal-derived products might be promising for wound repair and tissue regeneration. Periplaneta americana, known as a kind of cockroach, and a patent drug (namely Kangfuxin Liquor) made of P. americana have been used for the treatment of various ulcers and wounds in China without scar, which is of great impression. However, what substances are responsible for its pronounced effects remains unknown, which prohibits further clinic applications of Kangfuxin Liquor. We have been interested in insect chemistry and made great achievements in this aspect in recent years. To secure the efficacy of P. americana, several extracts or fractions out of P. americana were prepared and biologically evaluated using several assays closely associated with wound repair. The results showed that some fractions are active and helpful for wound repair. With these in hand, our isolation of P. americana afforded more than 40 compounds with diverse or intriguing structures. Further bioassays revealed that some compounds are active against inflammation, collagen production, and Wnt/β-catenin expression, indicating that rational substances might be present in P. americana. HPLC profiling indicates that substances, in particular of polar substances, are rich in the extract of P. americana. It is therefore necessary to clarify their structures, their biological roles in wound repair focusing on inflammation, proliferation and granulation, and remodeling. It is also necessary to understand how these biologically active substances regulate wound healing and tissue regeneration. These will be the mission of this project. Our fruitful production on this insect will help to gain a deep insight into chemical profiling of P. americana and will probably provide a drug lead in wound healing field beneficial for future drug development.
