水蛭地龙提取液通过VEGF-Notch/DLL4信号通路调控随意皮瓣成活的机制研究

项目名称： 水蛭地龙提取液通过VEGF-Notch/DLL4信号通路调控随意皮瓣成活的机制研究

项目编号： No.81503397

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 林丁盛

作者单位： 温州医科大学

项目金额： 18万元

中文摘要： 随意皮瓣常用于临床组织缺损修复，但其长宽比例受限制，远端容易出现缺血坏死，影响其临床应用。如何在增加随意型皮瓣长宽比例的同时，改善皮瓣微循环及血运，保证较高的成活率，对扩大其临床应用范围有重要意义。前期我们研究发现水蛭地龙提取液可以促进VEGF的表达，Notch4和DLL4表达下降，从而促进皮瓣存活，但VEGF-Notch/DLL4具体调控机制未明。本项目拟建立SD大鼠超长随意皮瓣模型，以水蛭地龙提取液作为干预手段，VEGF-Notch/Delta信号通路为研究切入点，通过组织病理、细胞分子生物、蛋白、基因芯片等技术深入探讨活血药物治疗下皮瓣的Notch、DLL4、VEGF、NICD、Hes、Hey等为主导的基因表达和调控的变化，确立此类药物治疗下随意皮瓣的相关基因差异表达谱和若干分子靶标，阐明其分子作用机制，为进一步临床应用提供理论支持和实验依据。

中文关键词： 随意皮瓣；信号通路；水蛭地龙提取液；大鼠模型

英文摘要： Random skin flap is very common used in the tissue repair, however, the limitation of its length/width ratio and its ischemic necrosis at distal end hinder its clinical application.It is valuable to enhance its length/width ratio and improve its blood supplement. Our previous studies found that traditional Chinese medicine of Shuxuetong injection significantly enhance the expression of VEGF and inhibit the expression of Nocth4 and DLL4 to improve the survivorship random skin flap. In this project, we use traditional Chinese medicine of Shuxuetong injection to treat random flap in SD rat model (modified McFarlane method), the VEGF-Notch/Dll4 signaling pathway will be investigated. The survival of flap will be observated；Immunohistochemical staining, Western Blot, Real-Time PCR, Protein and Genetic chip will be applied. the key protein and gene expression of Notch, DLL4,VEGF, NICD, Hes, Hey will aslo be investigated. We will establish related gene expression profiles and a number of differences in the molecular target of random flap,clarify the molecular mechanism of Shuxuetong injection to promote random flap survival, and provide theoretical and experimental evidence to support its further clinical application.

英文关键词： random skin flap;Signaling pathway;traditional Chinese medicine Shuxuetong injection;rat model