从“肠源性色氨酸代谢-中枢小胶质细胞极化”角度揭示通腑中药大黄治疗缺血性中风的科学内涵

“上病下治”与现代医学“脑-肠”轴学说不谋而合，以此为基础的“肠源性代谢物-中枢小胶质细胞”互动反应，有望成为揭示中医通腑法治疗中风科学内涵的关键突破口。中风发生后，肠源性色氨酸代谢紊乱，其代谢/合成关键酶IDO1/WARS1异常表达，通过TREM-1/TREM-2/SYK放大炎症信号，加重中枢炎性损伤。大黄作为中医通腑法治疗中风的要药，临床上广泛用于中风急性期患者的治疗。课题前期研究发现大黄可显著改善肠道菌群结构及肠道通透性，下调中风后IDO1、TREM-1及SYK的表达。结合以上工作基础，本项目提出以“肠源性色氨酸代谢-中枢小胶质细胞极化”为桥梁，大黄可通过调节IDO1/WARS1等色氨酸代谢关键酶，进而影响肠源性色氨酸代谢及其下游TREM-1/SYK信号传递，最终改善神经炎症，发挥抗脑缺血作用的科学假说。有望完善大黄治疗急性期中风的作用机理，进一步揭示中医通腑法治疗中风的科学内涵。

"Upper disease, lower treatment" coincides with the theory of "brain-gut" axis in modern medicine. The interactive reaction of "gut derived metabolites-central microglia" based on this theory is expected to become a key breakthrough to reveal the scientific connotation of traditional Chinese medicine Tongfu method in the treatment of stroke. After stroke, the metabolism of intestinal tryptophan is disturbed, and IDO1/WARS1, the key enzyme of metabolism/synthesis, are abnormally expressed. The inflammatory signal is amplified by TREM-1/TREM-2/SYK, which aggravates the central inflammatory injury. Rhubarb is widely used in the treatment of patients with acute stroke as an important medicine in the treatment of stroke. Previous studies found that rhubarb can significantly improve the compositions of intestinal flora and intestinal permeability, and down-regulate the expression of IDO1, TREM-1 and SYK after stroke. Based on the above results, this project proposes a scientific hypothesis that rhubarb can regulate the expressions of IDO1/WARS1, and then affect intestinal tryptophan metabolism and its downstream TREM-1/SYK signal transmission, ultimately improve neuroinflammation and play an anti-cerebral ischemia role by taking "intestinal tryptophan metabolism central microglia polarization" as a bridge. It is expected to enrich the mechanism of Rhubarb in the treatment of acute stroke, and further reveal the scientific connotation of “Tongfu” traditional Chinese medicine in the treatment of stroke.