基于免疫代谢串扰探讨金匮肾气丸调节BAT-ATM线粒体转移治疗糖尿病的作用机制

恢复能量代谢平衡是治疗糖尿病的重要研究方向，棕色脂肪组织（BAT）在其中发挥了多效性调节作用。最新研究发现，M2型巨噬细胞通过线粒体跨细胞转移影响BAT功能活性，影响脂肪免疫代谢平衡。中医学“气归精，精归化”理论高度概括了物质与能量的转化联系，促进肾中精气交汇是调节糖尿病能量代谢失衡的治疗方向。既往研究发现，金匮肾气丸具有改善糖代谢紊乱、调节免疫、促进能量代谢的作用，申请人进一步发现金匮肾气丸能通过促进线粒体激活因子UCP-1、PGC-1α、PPARγ表达从而激活BAT活性。本项目聚焦免疫代谢串扰，采用micro-PET/CT、活体多光子显微成像、线粒体标记追踪等技术方法，通过体内、体外实验明确温肾化气、滋阴填精之金匮肾气丸干预后BAT-ATM交互作用及线粒体跨细胞转移机制，直观动态展示“精”、“气”交汇互化过程，为金匮肾气丸促进BAT活性进而调节糖尿病能量代谢提供科学依据。

Restoring energy metabolic homeostasis is an important research direction in the treatment of diabetes mellitus, in which brown adipose tissue (BAT) plays a pleiotropic regulatory role. Recent studies have revealed that M2 macrophages influence the functional activity of BAT through mitochondrial transcellular transfer, affecting the balance of adipose immunometabolism. The cycle from traditional Chinese medicine "qi depends on essence while essence transforms into qi" highly summarizes the transformation relationship between substance and energy, suggesting that promoting the exchange of essence and qi is the therapeutic direction for regulating energy metabolism imbalance and glucose metabolism disorder. Our preliminary studies have confirmed that Jingui Shenqi Wan(JGSQW) can activate BAT by promoting the expression of mitochondrial activators UCP-1, PGC-1α and PPARγ. This project focuses on local immunometabolic crosstalk and identifies the mechanism of BAT-ATM interaction and mitochondrial transcellular transfer after the intervention of JGSQW, which has functions of warming the kidney and transforming qi, nourishing yin and supplementing essence. The main research methods in this project bases on experiments in vitro and vivo, adopting micro-PET/CT, in vivo multi-photon microscopic imaging and mitochondrial marker tracing. This study can visually and dynamically demonstrate the overall process of the intersection of "essence" and "qi", and provide a scientific basis for the promotion of BAT activity by JGSQW, thereby regulating the imbalance of energy metabolism in diabetes mellitus.