SCFA/Resistin/NLRP3信号途径在肥胖相关椎间盘退变中的作用及机制研究

椎间盘退变（IDD）导致的下腰痛给社会带来沉重负担。肥胖在我国呈现流行趋势，已成为IDD最主要的高危因素之一。前期研究证实肥胖中异常高表达的关键脂肪因子Resistin参与髓核NLRP3炎性小体的活化，引起炎症反应过度激活，从而在IDD的发生机制中发挥重要作用。近年研究表明肠道菌群这一“隐藏的器官”通过合成SCFA在众多疾病发展中扮演重要角色，SCFA可调节Resistin活性异常进而与肥胖相关疾病存在着密切联系，但其在肥胖相关IDD中的作用机制研究鲜有报道。本课题拟从肠道微生态的角度入手，通过大体、组织、细胞和分子等多层面证实肠道菌群代谢产物SCFA通过调节Resistin-NLRP3炎性小体途径的过度激活，继而影响肥胖相关IDD的发生发展。并运用特异性手段干预SCFA/Resistin/NLRP3炎性小体信号途径，尝试缓解和逆转IDD，为肥胖相关IDD的防治策略提供新思路。

Low back pain resulted from intervertebral disc degeneration (IDD) brings heavy burden to the society. Obesity has a prevailing trend in China and is one of the most important risk factors for IDD. Previous studies have confirmed that the key adipokine resistin which is abnormally high expressed in obesity is involved in the activation of NLRP3 inflammasome in nucleus pulposus to over-activate the inflammatory response, playing an important role in the mechanism of IDD. Recent studies have shown that the gut microbiota as a "hidden organ" plays an important role in the development of many diseases by synthesizing SCFA. SCFA can regulate the abnormal activity of resistin and is closely related to obesity-related diseases, while its effects on obesity-related IDD is rarely reported. This study intends to start from the perspective of intestinal micro-ecology, and confirm the intestinal flora metabolite SCFA affects the development of obesity-related IDD by regulating the excessive activation of the Resistin-NLRP3 inflammasome pathway at the general, tissue, cellular and molecular levels. And we use specific means to intervene in the SCFA/Resistin/NLRP3 inflammasome signaling pathway and try to alleviate and reverse IDD, so as to provide new thoughts for the intervention and prevention strategies of obesity-related IDD.