肠道菌群紊乱通过SCFAs-GPR43-HDAC轴抑制Treg细胞分化介导CNP发病的机制研究

慢性非细菌性前列腺炎(CNP)是泌尿系统常见病，其发病率高、易复发，严重危害患者身心健康。文献及申请人发表的研究表明肠道菌群紊乱与CNP发病密切相关，但其影响CNP发生的具体机制尚不清楚。申请人前期预实验结果显示Treg细胞在CNP发病中起关键作用，并且CNP中肠道菌群代谢产物SCFAs及受体GPR43降低，其下游分子HDAC抑制减少，而后者也被发现在抑制Treg细胞分化中扮演重要角色。据此，我们提出假设：肠道菌群紊乱通过SCFAs-GPR43-HDAC轴抑制Treg细胞分化介导CNP发生。本课题拟采用FACS、GC-MS等方法，通过体内外实验探索：Treg细胞在CNP发病中的作用；SCFAs-GPR43-HDAC轴对CNP中Treg分化的调控作用；肠道菌群紊乱通过SCFAs-GPR43-HDAC轴调控CNP中Treg分化的机制。本课题有望为CNP发病机制提供新理论，为其防治提供新策略。

Chronic non-bacterial prostatitis (CNP) is a common disease of urinary system. Its incidence rate is high, and it is easy to relapse, which seriously endangers the patients’physical and mental health. The literature and our published study have shown that the disorder of gut microbiota is closely related to the onset of CNP, but the specific mechanism between them is still unclear. The applicant's preliminary results showed that Treg cell plays a key role in the pathogenesis of CNP, and the SCFAs, a group of metabolites from gut microbiota, as well as its receptor GPR43 in CNP was decreased. Also, the inhibition of HDAC, a downstream molecule of GPR43, was reduced. The HDAC was also found to play an important role in inhibiting the differentiation of Treg cell. Therefore, we hypothesized that the disturbance of gut microbiota could inhibit the differentiation of Treg cell through SCFAs-GPR43-HDAC axis to mediate the occurrence of CNP. In this study, FACS, GC-MS and other methods were used in vivo and in vitro experiments to explore: the role of Treg cell in the pathogenesis of CNP; the regulation of SCFAs-GPR43-HDAC axis on Treg cell differentiation in CNP; the mechanism of gut microbiota disturbance inhibiting Treg cell differentiation in CNP via SCFAs-GPR43-HDAC axis. This project is expected to provide a new theory for the pathogenesis of CNP and a new strategy for its prevention and treatment.