As one of the main types of secondary craniocerebral injury, the onset, progression, and prognosis of chronic subdural hematoma (CSDH) are closely related to the local inflammation of intracranial hematoma. Atorvastatin is reported to be effective in the conservative treatment of CSDH. This study aimed to clarify whether atorvastatin regulated the inflammatory responses in CSDH by interfering with the function of macrophages. The rat CSDH model was prepared by repeated intracranial blood injection with velocity gradient, and MRI was applied to calculate the intracranial hematoma volume. Changes in rat nerve functions were evaluated by foot-fault and Morris water maze tests. Flow cytometry was applied to detect the number of total macrophages and the percentage of M1 or M2 macrophages. The expression of inflammatory factors was examined by ELISA and western blot. Western bolt was applied to detect the expression of proteins involved in the colony-stimulating factor 1 receptor (CSF-1R) signaling pathway. Our results showed that atorvastatin significantly accelerated the absorption of hematoma and improved the nerve functions of CSDH rats. In addition, atorvastatin treatment effectively suppressed the expression of TNF-α, IL-6, and IL-8 and promoted the expression of IL-10. The total number of macrophages was decreased, and the percentage of M2 macrophages was increased in the intracranial hematoma following atorvastatin treatment. Furthermore, atorvastatin increased the levels of M2-related genes and surface markers in BMDMs stimulated by lipopolysaccharides and IFNγ, and activated the CSF-1R signaling pathway. In conclusion, our study shows that atorvastatin could alleviate the symptoms of CSDH and promote hematoma ablation by polarizing macrophages to M2 type and regulating the inflammatory responses.

作为继发性颅脑损伤的主要类型之一，慢性硬膜下血肿（CSDH）的发生、进展和预后与颅内血肿的局部炎症密切相关。据报道，阿托伐他汀对 CSDH 的保守治疗有效。本研究旨在阐明阿托伐他汀是否通过干扰巨噬细胞的功能来调节 CSDH 的炎症反应。采用速度梯度重复颅内血液注射制备大鼠CSDH模型，应用MRI计算颅内血肿体积。大鼠神经功能的变化通过足部故障和莫里斯水迷宫试验进行评估。应用流式细胞术检测总巨噬细胞数和M1或M2巨噬细胞的百分比。通过ELISA和蛋白质印迹检查炎症因子的表达。应用Western bolt 检测集落刺激因子1 受体（CSF-1R）信号通路相关蛋白的表达。我们的研究结果表明，阿托伐他汀显着加速了血肿的吸收，改善了 CSDH 大鼠的神经功能。此外，阿托伐他汀治疗有效抑制TNF-α、IL-6和IL-8的表达，促进IL-10的表达。阿托伐他汀治疗后颅内血肿中巨噬细胞总数减少，M2巨噬细胞百分比增加。此外，阿托伐他汀增加了脂多糖和 IFNγ 刺激的 BMDM 中 M2 相关基因和表面标志物的水平，并激活了 CSF-1R 信号通路。综上所述，