人参皂苷促进脑膜淋巴系统介导的血肿吸收治疗脑出血

血肿清除对治疗脑出血（ICH）至关重要。目前，尚缺乏旨在促进血肿吸收的药物治疗方法。脑膜淋巴系统作为脑部的排出通道，是一种潜在的治疗途径。人参皂苷（PNS）已被证明能促进外周淋巴管生成，有效减少ICH患者的血肿。然而，PNS对脑膜淋巴管（MLVs）的潜在药理作用尚不清楚。在本研究中，我们旨在探讨PNS对脑膜淋巴系统及ICH的影响。采用胶原酶诱导的ICH模型研究PNS的作用。通过行为学测试（包括改良神经功能缺损评分（mNSS）和足迹试验）及血肿体积评估神经功能和治疗效果。利用免疫组化染色检测MLVs的结构和引流功能。结合Visudyne脑池注射和红激光光转换技术进行MLVs的消融。采用RNA测序分析其作用机制。结果显示，ICH第14天后，脑膜淋巴引流功能增强，但未明显观察到淋巴管生成。此外，PNS进一步促进引流过程，同时诱导淋巴管生成。MLVs的光转换消融显著阻断了PNS改善神经功能和吸收血肿的效果。RNA测序发现PNS调控轴突发生和炎症反应，依赖完整的MLVs。其中，溶质载体家族17成员7（Slc17a7）和肿瘤坏死因子（Tnf）被认为是靶基因蛋白-蛋白相互作用网络中的瓶颈和枢纽节点。PNS可能通过增强淋巴管生成和脑膜淋巴引流功能，减轻炎症，促进神经功能恢复，从而为ICH的治疗提供新策略。这是首次系统研究PNS调控MLVs的作用，为PNS在ICH治疗中的应用提供了新见解。

Hematoma clearance is crucial for treating intracerebral hemorrhage (ICH). Currently, there is a lack of pharmacological therapy aimed at promoting hematoma absorption. Meningeal lymphatic system, as a drain of brain, is a potential therapeutic approach in ICH. Panax Notoginseng Saponins (PNS), proven to promote lymphangiogenesis in periphery, effectively reduces hematoma in ICH patients. However, the potential pharmacological effect of PNS on meningeal lymphatic vessels (MLVs) remains unknown.In this study, we aimed to investigate the impact of PNS on the meningeal lymphatic system and ICH.The collagenase-ICH model was conducted to investigate the effect of PNS. Behavioral tests, including modified neurological severity score (mNSS) and foot-fault test, and hematoma volume were used to estimate the neurological function and curative effect. The structure and drainage function of MLVs was detected by immunohistochemical staining. Visudyne intracisternal magna injection combined with red laser photoconversion was performed to ablate MLVs. RNA-sequencing was used to obtain mRNA profiles for mechanistic investigation.The meningeal lymphatic drainage function was enhanced after ICH on day 14 without obvious lymphangiogenesis. Additionally, PNS further facilitated the process of drain with simultaneously inducing lymphangiogenesis. Moreover, ablation of MLVs by photoconverting of visudyne significantly blocked the benefits of neurological deficits improvement and hematoma absorption conducted by PNS. Furthermore, RNA-sequencing revealed that PNS regulated axonogenesis and inflammation, relying on the intact MLVs. In which, solute carrier family 17 member 7 (Slc17a7) and tumor necrosis factor (Tnf) were identified as bottleneck and hub nodes of the protein-protein interaction network of target genes, respectively.PNS might be effective for ICH treatment by enhancing lymphangiogenesis and the meningeal lymphatic drainage function, thereby attenuating inflammation and promoting neurological recovery. The role of PNS in regulation of MLVs was investigated for the first time. This study provides a novel insight for PNS in the medical therapy of ICH.