神经损伤与功能重建2026，Vol.21Issue(4)：187-193,212,8.DOI:10.16780/j.cnki.sjssgncj.20260188
胆红素通过调控小胶质细胞表型转化改善慢性缺血性脑白质损伤
Bilirubin Alleviates Chronic Ischemic White Matter Injury via Microglial Modulation
摘要
Abstract
Objective:To investigate the protective effects of bilirubin on white matter injury and cognitive impairment under chronic cerebral hypoperfusion,and to elucidate its association with the regulation of microglial functional states.Methods:A bilateral common carotid artery stenosis(BCAS)mouse model was employed to induce chronic cerebral hypoperfusion.Behavioral assessments,histological analyses,and single-cell transcriptomic profiling were integrated to systematically evaluate the effects of bilirubin on white matter integrity and the inflammatory microenvironment.Results:Bilirubin treatment significantly improved learning,memory,and recognition abilities in BCAS mice,accompanied by marked attenuation of demyelination and structural disruption in the corpus callosum.Single-cell transcriptomic and histological analyses revealed that bilirubin suppressed inflammatory and immune-response-related transcriptional programs,thereby inhibiting the inflammatory and phagocytic activation of microglia.Trajectory inference and transcription factor regulatory analyses demonstrated that bilirubin redirected microglial state transitions away from inflammation-associated terminal states toward homeostatic and repair-related phenotypes.This shift was characterized by enhanced TGF-β-associated regulatory networks and concurrent suppression of interferon signaling pathways.Conclusion:Bilirubin effectively alleviates white matter injury and cognitive dysfunction induced by chronic cerebral hypoperfusion by reshaping microglial functional states and the inflammatory microenvironment.关键词
胆红素/小胶质细胞/慢性脑缺血/脑白质损伤/炎症反应Key words
bilirubin/microglia/chronic cerebral ischemia/white matter injury/inflammation分类
医药卫生引用本文复制引用
梅智诚,庞晓伟,陈恋,初云惠,周罗绮,秦川,田代实..胆红素通过调控小胶质细胞表型转化改善慢性缺血性脑白质损伤[J].神经损伤与功能重建,2026,21(4):187-193,212,8.基金项目
国家自然科学基金(小胶质细胞TREM2-PLIN5调控脂滴-线粒体互作参与脑缺血白质损伤后髓鞘修复的分子机制,No.82371404 （）
血管相关小胶质细胞的脂质感应和清除途径:慢性低灌注脑白质损伤的调控新靶点?No.82271341 （）
FSAP-LOX1介导的内皮细胞氧化应激损伤在微循环"无复流"中的作用研究,No.82301510) （）
