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.
