研究动态
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三七皂苷促进脑膜淋巴系统介导的脑出血血肿吸收。

Panax Notoginseng Saponins promotes the meningeal lymphatic system-mediated hematoma absorption in intracerebral hemorrhage.

发表日期:2024 Oct 11
作者: Zhe Yu, Xi-Ya Yang, Yi-Qing Cai, En Hu, Teng Li, Wen-Xin Zhu, Yao Wu, Qiu-Ju Yan, Zhi-Lin Li, Quan Chen, Zhuan Pei, Fei Zheng, Yang Wang, Tao Tang
来源: PHYTOMEDICINE

摘要:

血肿清除对于治疗脑出血(ICH)至关重要。目前,缺乏旨在促进血肿吸收的药物治疗。脑膜淋巴系统作为大脑的引流管,是脑出血的潜在治疗方法。三七皂苷(PNS)被证明可以促进外周淋巴管生成,有效减少脑出血患者的血肿。然而,三七总皂苷对脑膜淋巴管(MLV)的潜在药理作用仍不清楚。本研究旨在探讨三七总皂苷对脑膜淋巴管系统和脑出血的影响。采用胶原酶-ICH模型来研究三七总皂苷对脑膜淋巴管系统和脑出血的影响。三七总皂苷。采用行为测试,包括改良神经严重程度评分(mNSS)和足错误测试以及血肿体积来评估神经功能和疗效。通过免疫组化染色检测MLV的结构和引流功能。进行 Visudyne 脑池内注射联合红色激光光转换来消融 MLV。利用RNA测序获得mRNA谱以进行机制研究。ICH后第14天脑膜淋巴引流功能增强,但没有明显的淋巴管生成。此外,三七总皂苷进一步促进引流过程,同时诱导淋巴管生成。此外,通过visudyne光转换消融MLV显着阻碍了PNS改善神经功能缺损和血肿吸收的益处。此外,RNA 测序表明,PNS 依赖于完整的 MLV 来调节轴突发生和炎症。其中,溶质载体家族17成员7(Slc17a7)和肿瘤坏死因子(Tnf)分别被确定为靶基因蛋白质-蛋白质相互作用网络的瓶颈和枢纽节点。PNS可能通过增强淋巴管生成和增强淋巴管生成来有效治疗ICH。脑膜淋巴引流功能,从而减轻炎症并促进神经功能恢复。首次研究了三七总皂苷 (PNS) 在 MLV 调节中的作用。这项研究为 ICH 的药物治疗中的三七总皂苷 (PNS) 提供了新颖的见解。版权所有 © 2024。由 Elsevier GmbH 出版。
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.Copyright © 2024. Published by Elsevier GmbH.