小胶质细胞炎性活化在系统性红斑狼疮抑郁的作用及机制研究

Previous studies of our research group revealed the high occurrence of depression in SLE patients, the high expression of inflammatory factors in the cerebrospinal fluid, and the activation of microglia in MRL/lpr mice. Thus, during the development of SLE, we proposed that the activation of microglia could prompt the occurrence of depression through the regulation of abnormal 5-HT metabolism in ganglionic neurons. This project firstly tried to analyze the correlation between the depression in SLE patients and the inflammatory factors in the cerebrospinal fluid, and then the correlation between the depression of MRL/lpr mice and the activation of microglia. On this basis, we analyzed whether microglia would promote the development of depression through the release of IDO which led to the abnormal 5-HT metabolism in ganglionic neurons. Finally, we treated the mice with Minocycline, an inhibitor of microglial activation, and explored the effects. This project provided the theoretical basis to understand the mechanism of SLE patients' depression and the data support to seek new treatments.

小胶质细胞的激活参与抑郁的发生。课题组前期研究发现SLE患者抑郁发生率高，脑脊液炎性因子高表达，MRL/lpr鼠存在小胶质细胞活化。因此提出SLE的发病过程中小胶质细胞活化可通过调节神经元内5-HT代谢异常，促进SLE抑郁的发生。本项目拟首先分析SLE患者抑郁与脑脊液炎性因子之间的相关性，接着分析MRL/lpr鼠抑郁与小胶质细胞活化的关系；在此基础上分析小胶质细胞是否通过释放IDO导致神经元内5-HT代谢异常，促进抑郁的发生；最后运用抑制小胶质细胞活化干预药物米诺环素等处理MRL/lpr鼠，观察其对抑郁的治疗作用。此项目研究可为阐明SLE患者抑郁的机制提供理论依据，为寻找SLE抑郁的治疗方法提供数据支持

先前研究已表明小胶质细胞的激活参与抑郁的发生。课题组前期研究发现SLE患者抑郁发生率高，脑脊液炎性因子高表达，MRL/lpr鼠存在小胶质细胞活化。因此提出SLE的发病过程中小胶质细胞活化可通过调节神经元内5-HT代谢异常，促进SLE抑郁的发生。本项目在已有的工作基础上，通过收集SLE抑郁及非抑郁患者病例资料及脑脊液标本，分析SLE患者抑郁与脑脊液炎性因子之间的相关性，发现SLE抑郁患者包括leptin、IL-28A、IL-15R等多种炎症因子表达异常；接着分析MRL/lpr鼠抑郁与小胶质细胞活化的关系；在此基础上分析小胶质细胞是否通过释放IDO导致神经元内5-HT代谢异常，促进抑郁的发生；最后运用抑制小胶质细胞活化干预药物米诺环素等处理MRL/lpr鼠，观察其对抑郁的治疗作用。此项目研究可为阐明SLE患者抑郁的机制提供理论依据，为寻找SLE抑郁的治疗方法提供数据支持。.研究结果共发表SCI期刊收录论文10篇，共培养研究生3名。