中文摘要
骨代谢异常是导致强直性脊柱炎(AS)患者残疾的重要因素,而西医治疗手段有限。名老中医焦树德教授的补肾强督治偻方治疗AS具有抗炎、调节骨代谢作用,可改善AS影像学进展,但具体机制不清。肠道菌群与IL-23/Th17炎症轴的相互作用构成了肠道免疫的核心机制,对AS骨代谢有调控作用。本研究沿着“肠道菌群—IL-23/Th17炎症轴—骨代谢”线性机制图,首先采用临床横断面研究筛选AS特异性肠道菌群,并验证其与IL-23/Th17炎症轴的关系;其次构建基于HLA-B27/β2-m双转基因的改良AS动物模型,体内实验探讨补肾强督治偻方通过肠道免疫调控AS骨代谢的作用机制;最后,鉴于IL-23/Th17炎症轴介导的肠道免疫对肠道菌群参与AS骨代谢调控的桥接作用,我们通过体外实验深入探讨补肾强督治偻方通过该轴调控骨代谢的信号转导机制。本研究通过递进深入的三个层次实验方案初步揭示中药复方治疗AS的科学内涵。
英文摘要
Abnormal bone metabolism is the main factor of disability in Ankylosing Spondilitis (AS). However, to date, there is no effective method to relieve or block it. Bushen-Qiangdu-Zhilv Decoction (BQZ) , which was established by Prof. Shu-De Jiao who is a well-known traditional Chinese medicine master in Rheumatology, has been demonstrated to be effective in relieving clinical symptoms, signs and inflammatory activity indicators of AS patients. Moreover, effects of BQZ on bone metabolism regulation and imaging improvement have also been reported. But the mechanism is unclear. Intestinal flora and IL-23 / Th17 axis interact and influence each other, which constitute a core part of intestinal immune mechanism and regulate the bone metabolism in AS. Based on the “intestinal flora- IL-23 / Th17 axis-bone metabolism” linear mechanism, we will firstly clarify the relationship between intestinal flora and IL-23 / Th17 axis in AS with cross-sectional study. Secondly, we will construct a modified AS animal model based on HLA-B27/β2 microglobulin transgenic rat. The effects of BQZ on bone metabolism through IL-23 / Th17 axis mediated-intestinal immune will be further examined. As IL-23/Th17 axis mediated-intestinal immune has a bridging role in intestinal flora and bone metabolism, we will explore the cellular signal transduction mechanism underlying BQZ regulation of the abnormal bone metabolism mediated by IL-23 / Th17 axis with further vitro study. These three researches are going to, to some extent, demonstrate the scientific connotation of anti-AS effects of the effective Chinese Medical formula by in-depth logic chains.
