基于肠道菌群调控TREM-1研究小胶质细胞炎症反应激活致糖尿病并发抑郁症前额叶皮质突触可塑性损伤机制及中药干预

糖尿病并发抑郁（DD）是危害人类健康的重大疾患，致死率高。前额叶皮质损伤与DD发生密切相关，但机制未明，国内外尚无报道。肠道菌群对小胶质细胞及突触结构和功能的调节都发挥重要作用，TREM-1是新发现的炎症触发受体，TREM-1能激活前额叶皮质小胶质细胞NLRP3炎症小体异常，触发炎症，从而调节突触可塑性。课题组前期发现，DD大鼠前额叶皮质损伤严重，TREM-1含量升高。因此，本课题拟综合运用Illumina 高通量测序技术、膜片钳、HCS等现代技术，通过在体与体外研究，探讨“糖尿病状态下，肠道菌群异常，TREM-1激活，调控NLPR3炎症小体释放，触发炎症反应，导致突触可塑性损伤，进而DD的发生。”的分子机制，并采用“滋阴益气、化瘀解郁”的治法方药干预，为中药防治DD的研究提高新的思路与靶点。

Diabetes mellitus complicated with depression (DD) is a major health hazard with high mortality.Prefrontal cortex injury is closely related to the occurrence of DD, but the mechanism is unknown and has not been reported at home and abroad. Intestinal flora plays an important role in the regulation of microglia and synaptic structure and function.Trem-1 is a newly discovered inflammatory trigger receptor, and trem-1 can activate abnormal NLRP3 inflammasome, trigger inflammation to regulate synaptic plasticity process of prefrontal cortex microglia.In the early stage, the research group found that the prefrontal cortex of DD rats was severely damaged and trem-1 content was increased.Therefore, this project intends to comprehensively apply Illumina high throughput sequencing technology, patch clamp,HCS and other modern technologies to study in vivo and in vitro, and to explore "under the condition of diabetes,abnormal intestinal flora,the activation of trem-1 and abnormal NLPR3 inflammatory corneosomes, and then trigger the inflammatory response, leading to synaptic plasticity damage, and the occurrence of DD.In order to improve the research of prevention and treatment of DD by traditional Chinese medicine.