脑出血后非神经元细胞特异性死亡途径及其对血脑屏障与白质结构的影响
Non-Neuronal Cell-Specific Death Pathways after Intracerebral Hemorrhage and Their Impact on the Blood-Brain Barrier and White Matter Structure
摘要: 脑出血(Intracerebral Hemorrhage, ICH)属于致死致残率颇高的脑血管疾病类别，其继发性损伤机制较为复杂，截至目前尚无有效的治疗方法。传统研究大多将目光集中在神经元损伤方面，但是近些年有证据显示，非神经元的支持细胞的凋亡在血脑屏障(Blood-Brain Barrier, BBB)的破坏以及白质(White Matter, WM)的损伤进程中起关键作用。本综述全面阐述脑出血后的脑微血管内皮细胞(Brain Microvascular Endothelial Cells, BMECs)、周细胞、星形胶质细胞以及少突胶质细胞这类非神经元细胞出现特异性程序性死亡的分子机制，重点突出铁过载和脂质过氧化所驱动的铁死亡在其中担当的关键枢纽角色。这些细胞的死亡并非单独发生的情形，而是借助炎症因子、趋化因子(比如CXCL10，LCN2相关的)等介质构建起复杂的多细胞相互作用网络，进而致使死亡信号得以放大并传播，从而共同使得神经血管单元(Neurovascular Unit, NVU)的崩溃状况更为严重。文章进一步探究针对此类细胞死亡通路的潜在治疗策略，比如抑制铁死亡、调节水通道蛋白AQP4的极性、增强IL-10信号。最后，指出当下研究在细胞特异性解析以及时空动态观测领域存在的技术短板，并对未来通过融合多组学技术、纳米药物递送以及多靶点联合治疗等方式促使脑出血治疗策略从“以神经元为中心”向“对神经血管单元进行整体保护”的范式转变进行展望，进而为实现精准医疗提供新的视角。
Abstract: Intracerebral hemorrhage is one of the cerebrovascular diseases with the highest rates of mortality and disability, and its secondary injury mechanisms are complex, with effective therapies currently lacking. Traditional research has primarily focused on neuronal damage; however, recent evidence indicates that the death of non-neuronal support cells plays a central role in blood-brain barrier disruption and white matter injury. This review systematically elucidates the molecular mechanisms of specific programmed cell death in non-neuronal cells—such as brain microvascular endothelial cells, pericytes, astrocytes, and oligodendrocytes—following intracerebral hemorrhage, with particular emphasis on the critical role of ferroptosis driven by iron overload and lipid peroxidation. The death of these cells is not an isolated event but forms a complex multicellular interaction network through mediators such as inflammatory factors and chemokines (e.g., CXCL10, LCN2), leading to the amplification and propagation of death signals and collectively exacerbating the collapse of the neurovascular unit. The article further explores potential therapeutic strategies targeting these cell death pathways, including inhibiting ferroptosis, regulating the polarity of aquaporin-4 (AQP4), and enhancing IL-10 signaling. Finally, it highlights the current technical limitations in cell-specific analysis and spatiotemporal observation, and prospects future paradigm shifts in ICH treatment strategies from “neuron-centric” approaches to “comprehensive neurovascular unit protection” through the integration of multi-omics technologies, nanodrug delivery, and multi-target combination therapies, thereby providing novel perspectives for precision medicine.
文章引用：郭汉龙, 黄泽村, 叶欣浩, 张加劲, 罗穆云. 脑出血后非神经元细胞特异性死亡途径及其对血脑屏障与白质结构的影响[J]. 临床医学进展, 2026, 16(2): 2850-2863. https://doi.org/10.12677/acm.2026.162697

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