长铺玉津汤通过调节脂质代谢和微胶质细胞极化缓解抽动秽语综合征：TREM2/NF-κB信号轴的参与作用

Abstract

Background:Changpu Yujin Decoction (CPYJD) has been clinically utilized for more than ten years as an effective herbal formula for Tourette syndrome (TS). However, the exact mechanism by which CPYJD treats TS via modulating lipid metabolism and microglia (MG) polarization remains unclear.Methods:A combination of in vivo and in vitro experiments was employed. A total of 72 three-week-old Sprague–Dawley (SD) rats were divided into a control group (n= 12) and a modeling group (n= 60). After successful model establishment, the modeled rats were randomly divided into five groups (n= 12 per group): the model group, the tiapride group, and the low-dose, medium-dose, and high-dose Changpu Yujin Decoction (CPYJD-L, CPYJD-M, and CPYJD-H, respectively) groups. All groups were administered the corresponding treatments for 28 consecutive days, and therapeutic efficacy was evaluated by behavioral scoring after the intervention. Neuronal morphology and myelin structure were observed by hematoxylin–eosin (HE) staining, Nissl staining, and transmission electron microscopy (TEM). The expression of lipid metabolism- and microglial phenotype-related indicators in each group was detected by immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), biochemical assays, reverse transcription quantitative PCR (RT-qPCR), and Western blotting (WB). In addition, lipidomics analysis was performed to identify differential lipid metabolites. For the in vitro experiments, triggering receptor expressed on myeloid cells 2 (TREM2) was knocked down in BV2 cells using small interfering RNA (siRNA), and inflammation was induced by lipopolysaccharide (LPS). The cells were divided into a control group, an LPS group, a CPYJD-medicated serum group, a TREM2 knockdown group, and a TREM2 knockdown plus CPYJD-medicated serum group. Cell morphology was observed under a microscope, and lipid metabolism- and microglial phenotype-related indicators in each group were detected by immunofl