目的：探讨胆红素在慢性脑缺血条件下对白质损伤和认知功能障碍的保护作用及其与小胶质细胞 表型转化的关系。方法：采用双侧颈总动脉狭窄（BCAS）小鼠模型，结合行为学、组织学及单细胞转录组 学分析，系统评估胆红素对脑白质损伤及炎症微环境的影响。结果：胆红素给药显著改善BCAS小鼠的 学习记忆和识别能力，并减轻胼胝体白质脱髓鞘程度。单细胞转录组学分析及免疫荧光染色显示，胆红 素显著下调炎症和免疫应答相关转录程序，抑制小胶质细胞的炎症与吞噬激活状态。轨迹推断和转录因 子调控分析表明，胆红素改变小胶质细胞状态转变方向，使其由炎症相关终末状态偏移至稳态及修复相 关状态，并伴随TGF-β相关调控网络增强和干扰素信号抑制。结论：胆红素通过重塑小胶质细胞功能状 态和炎症微环境，有效缓解慢性脑缺血所致的白质损伤并改善认知功能。

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.