中国中西医结合杂志2025，Vol.45Issue(6)：706-713,8.DOI:10.7661/j.cjim.20250411.007
当归芍药散调控EPO/PPAR-γ/AXL通路增强小胶质细胞吞噬改善血管性认知障碍
Danggui Shaoyao San Alleviates Vascular Cognitive Impairment by Enhancing Microglial Phagocytosis through Modulation of the EPO/PPAR-γ/AXL Pathway
摘要
Abstract
Objective To investigate the effect of Danggui Shaoyao San(DSS)on vascular cognitive impairment(VCI)and erythropoietin(EPO)/peroxisome proliferator-activated receptor gamma(PPAR-γ)/AXL receptor tyrosine kinase(AXL)pathway.Methods Forty SD male rats were randomly divided into the sham operation group(Sham group),model group(VCI group),low-dose DSS group(5 g/kg),high-dose DSS group(10g/kg),and nimodipine(NMP group,9.45 mg/kg),with 8 rats in each group.The VCI model was established by the two-vessel occlusion(2-VO)method in all groups except the Sham group,and the intervention was given immediately for four weeks,with the Sham and VCI model groups received equivalent volumes of saline.After that,Morris water maze was used to evaluate the learning memory ability of rats.HE staining was used to detect hippocampal tissue damage.Luxalfast blue staining was used to detect hippocampal myelin damage,and immunofluorescence staining was used to detect the activation of microglia and levels of myelin-related proteins.Quantitative real-time PCR(qRT-PCR)was applied to detect the expression of M2 polarization markers and phagocytosis-related genes of microglia,and ELISA was used to detect inflammatory factors.Western Blot was used to determine the expression of EPO pathway-related proteins in hippocampus.Results Morris water maze test results showed that,compared with the model group,the rats in the high-dose DSS group showed increase in the number of platform crossing and the time in target quadrant,whereas decrease in the escape latency(P＜0.01).Furthermore,high-dose DSS decreased levels of IL-6,TNF-α and MCP-1 in hippocampus(P＜0.05).qRT-PCR results showed that the expression of M1 polarization marker CD68 was decreased while the expression of M2 polarization markers CD206 and Arg-1 were increased in high-dose DSS group(P＜0.01,P＜0.05).Western Blot analysis revealed that high-dose DSS treatment significantly upregulated the expression of EPO,PPAR-γ,and AXL proteins compared to the model group(P＜0.01).Conclusion DSS improved hippocampal microglial phagocytosis by regulating EPO/PPAR-γ/AXL pathway,and promoted the polarization of microglia from M1 to M2,thus reducing neuroinflammation and then improving VCI.关键词
血管性认知障碍/当归芍药散/小胶质细胞/促红细胞生成素/过氧化物酶体增殖物激活受体γ/AXL受体酪氨酸激酶/中药复方/中西医结合Key words
vascular cognitive impairment/Danggui Shaoyao San/microglia/erythropoietin/peroxisome proliferator-activated receptor gamma/AXL receptor tyrosine kinase/Chinese herbal compound/integrative medicine引用本文复制引用
李翔,袁宁宁,徐莹,苏越,成小兰..当归芍药散调控EPO/PPAR-γ/AXL通路增强小胶质细胞吞噬改善血管性认知障碍[J].中国中西医结合杂志,2025,45(6):706-713,8.基金项目
国家自然科学基金面上项目(No.82274218) （No.82274218）
江苏省研究生科研创新计划项目(No.KYCX24_2335) （No.KYCX24_2335）
