美洲大蠊提取液对大鼠难愈合创面TGF-β1/Smads通路、ECM及DED的调控研究

Chronic nonhealing wound, known as skin ulcer, has been become one of the public health problems, and there is no effective, simple and inexpensive treatment for this disease in clinical practice at the present. The lastest studies indicated that the TGF-β1/Smads signaling pathway plays the important role in wound healing process,and growth factors regulate the synthesis and degradation of extracellular matrix and cell proliferation and apoptosis are the key to wound healing. Our previous study found that Periplaneta Americana extract can promote chronic nonhealing wound repair and enhance the expression of VEGFmRNA on tissue, but the mechanism is not completely understood. This project, based on previous studies, aims to research the Periplaneta Americana extract regulate ECM and cell apoptosis on the expression of proteins or genes during the process of chronic nonhealing wound healing in rats by use of the electron microscopy, the Western Blot, the Real-time PCR，the Immunohistochemistry and so on. which will further illuminate the molecular mechanism of the Periplaneta Americana extract in promoting chronic nonhealing wound repair based on the TGF-β1/Smads signaling pathway, ECM and cell apoptosis, and provide a reliable treatment method and theoretical basis for clinical application periplaneta Americana extract to prevent and treat the chronic nonhealing wound.

体表慢性难愈合创面 (俗称皮肤溃疡)已成为危害人类健康的公共问题，目前临床上仍缺乏有效简廉的治疗方法。最新研究表明，TGF-β1/Smads信号通路在难愈合创面的愈合过程中发挥着相当重要的作用，而生长因子调节细胞外基质的合成与降解以及细胞增殖与凋亡是伤口愈合的关键。课题组前期研究发现美洲大蠊提取液能促进难愈合创面愈合，并能提高组织中VEGFmRNA的表达，但促愈机制尚未完全清楚。此项目在前期研究的基础上，分别运用电镜技术、Western Blot、Real-time PCR、免疫组化等方法，研究美洲大蠊提取液对慢性难愈合创面愈合过程中有关细胞外基质及细胞凋亡等的蛋白和基因表达的调控，以期从TGF-β1／Smads信号通路、ECM及细胞凋亡角度，进一步阐明美洲大蠊提取液促进慢性难愈合创面修复的分子机制，为临床推广应用美洲大蠊提取液防治慢性难愈合创面提供一种可靠的治疗方法和理论依据。

体表慢性难愈合创面目前临床上仍缺乏有效简廉的治疗方法。本课题组主运用电镜技术、Western Blot、Real-time PCR、免疫组化等方法，研究美洲大蠊提取液对慢性难愈合创面愈合过程中有关细胞外基质及细胞凋亡等的蛋白和基因表达的调控，试验结果表明美洲大蠊提取液能有效提高大鼠难愈合创面桥粒、微丝等超微结构的表达，前中期Ⅰ/Ⅲ型胶原蛋白的表达，降低胶原蛋白的过度表达而减少瘢痕形成；能高效调控凋亡基因的趋势化、提高透明质酸、蛋白聚糖的表达，有效降低Smad6、Smad7的表达，增加Smad9的表达，减少Smad7的自身磷酸化，从而减弱Smad7对TGF-β1信号转导的抑制，进一步阐明美洲大蠊提取液促进慢性难愈合创面修复的分子机制，为临床推广应用美洲大蠊提取液防治慢性难愈合创面提供一种可靠的治疗方法和理论依据。