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基于宏基因组学探讨肾病II号方防治IgA肾病单纯性血尿的作用机制

基于宏基因组学探讨肾病II号方防治IgA肾病单纯性血尿的作用机制
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  • 批准号:81673960
  • 批准年度: 2016年
  • 学科分类:中医内科(H2708) |
  • 项目负责人:孙晓敏
  • 负责人职称:副教授
  • 依托单位:南方医科大学
  • 资助金额:55万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: 宏基因组学;肾病;号方;IgA;肾病单纯性血尿
  • 英文关键词:Immunoglobulin A nephropathy (IgAN);asymptomatic hematuria;metagenomics;gut microbiota;Shenbingerhao

项目摘要

中文摘要

血尿为IgA肾病(IgAN)最常见的临床症状,然而其治疗手段有限。诸多证据表明:肠道微生物参与了IgAN的发病过程,但其机制迄今尚未阐明。我们前期研究发现IgAN单纯性血尿患者肠道菌群结构发生显著的变化,而经过中药复方“肾病II号方”治疗后可使其肠道菌群结构异常向正常水平恢复。推测肠道菌群紊乱可能在IgAN单纯性血尿发生发展中起到重要作用。本项目拟在前期的基础上,采取临床研究结合动物实验,以肾病II号方为干预手段,首先应用宏基因组学方法,明确IgAN单纯性血尿肠道菌群的变化特征;其次,利用无菌小鼠结合粪菌移植技术,观测免疫功能、红细胞功能、微血管内皮细胞以及肾小球细胞相关分子表达情况等指标,探讨肠道微生物对IgAN单纯性血尿发生的影响;最后,利用生物信息学方法进行整合分析,阐明肠道菌群稳态失衡在IgAN单纯性血尿发生中的作用及“肾病II号方”的调节机制,为其临床应用提供实验依据。

英文摘要

Hematuria is the most common symptom of Immunoglobulin A nephropathy (IgAN). However, there is lacking effective treatment. Previous studies had presented evidence that gut microbiota play a role in the occurrence of IgAN, but the etiology and the mechanism of its development require further elucidation. A previous investigation by us had found that remarkable changes took place in the construction of gut microbiota among the patients with IgAN asymptomatic hematuria, and it could be recover by the treatment of Shenbingerhao Decoction, which had been developed by our group and had been showed significant effect for asymptomatic hematuria. Accordingly, we theorize that the abnormal gut microbiota may play an important role in the occurrence of IgAN asymptomatic hematuria. Basing on the previous study, in this project, we aim to investigate the change characteristics of gut microbiota in patients with IgAN asymptomatic hematuria clinically, and in the making animal model of the mouse with IgAN asymptomatic hematuria, by the intervention means of Shenbingerhao Decoction, and the technology of metagenomics. Secondly, we will investigate how the gut microbiota impact the occurrence of IgAN asymptomatic hematuria, by applying the germ free mice and the fecal microbiota transplantation and observing the immune function, erythrocyte function, and related molecules of microvascular endothelial cell and glomerular cell. Eventually, conducting bioinformatics method for integrated analysis, we will ascertain how the unbalance of homeostasis in gut microbiota works in the impact of glomerular cells and red blood cells, and in the development of IgAN asymptomatic hematuria, confirm the regulation mechanism of gut microbiota in the treatment of IgAN asymptomatic hematuria by Shenbingerhao Decoction, intending to provide experiment evidence for clinical adoption.

评估说明

    国家自然科学基金项目“基于宏基因组学探讨肾病II号方防治IgA肾病单纯性血尿的作用机制”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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