基于益肾散结复方对MSCs归巢和旁分泌作用探讨益肾散结配伍的科学内涵

项目名称： 基于益肾散结复方对MSCs归巢和旁分泌作用探讨益肾散结配伍的科学内涵

项目编号： No.81503441

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： 张晓凤

作者单位： 陕西省中医药研究院

项目金额： 18万元

中文摘要： 慢性肾脏病是严重危害人类身体健康的重大疾病，其进展至终末期肾病的共同病理状态是肾间质纤维化，探索治疗肾间质纤维化的有效手段及其机制一直是相关领域的热点科学问题。肾复康Ⅱ号临床治疗肾间质纤维化有肯定的疗效，实验证实其具有促进移植后MSCs分泌抗纤维化因子HGF抑制肾间质纤维化的作用，但其确切机制及作用靶点尚不明确。本课题拟以肾复康Ⅱ号益肾散结的组方原则拆方，以SDF-1/CXCR4和HGF/c-Met为靶点，通过MSCs直接和SiRNA抑制受体表达后移植的方法，从不同时间点、不同水平研究复方组、益肾组、散结组、单纯移植组中SDF-1/CXCR4的差异表达及其对MSCs归巢的影响，HGF/c-Met的差异表达及其对MSCs旁分泌作用的影响，揭示益肾散结复方作用于MSCs归巢和旁分泌因子抗肾间质纤维化的机制，寻找益肾、散结药物的作用靶点，冀为阐明益肾散结配伍的科学内涵提供实验依据。

中文关键词： 益肾散结复方；间充质干细胞；归巢；旁分泌；肾间质纤维化

英文摘要： Chronic kidney disease is a major disease which can seriously harm to human health and its common pathological condition of progression to ESRD is renal interstitial fibrosis, so to explore effective means and mechanisms of treatment of renal fibrosis has been a hotspot scientific issue in related fields. Shenfukang Ⅱhave a positive effect in clinical treatment of renal interstitial fibrosis. The result of the preliminary experiment shows that yishen sanjie compound plays a role in promoting transplanted MSCs secretion HGF and inhibiting renal interstitial fibrosis. This project is intended to disassemble compound according to prescription form on the basis of “yishen sanjie”, and target SDF-1 and HGF, by the methods with MSCs transplantation, SiRNA inhibition of the expression of its receptor transplantation, from a different point and different level , We can study the differential expression on SDF-1/CXCR4 and effects on MSCs homing, and the differential expression on HGF/c-Met and effects on MSCs paracrine.The above results can reveal the mechanism of yishen sanjie compound on renal interstitial fibrosis by MSCs homing and paracrine and can find the targets of yishen theorem and sanjie theorem, providing with experimental evidence to illuminate the scientific connotation of yishen sanjie compatibility.

英文关键词： yishen sanjie compound;mesenchymal stem cells;homing;paracrine;renal interstitial fibrosis