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panax notoginseng saponins促进脑膜介导的脑膜介导的脑出血中的血肿吸收

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

影响因子:8.30000
分区:医学1区 Top / 药物化学1区 全科医学与补充医学1区 药学1区 植物科学1区
发表日期:2024 Dec
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

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理疗法。脑膜淋巴系统作为大脑的流失,是ICH中潜在的治疗方法。 Panax notoginseng皂苷(PNS)被证明可以促进周围淋巴管生成,有效地减少了ICH患者的血肿。然而,PNS对脑膜淋巴管(MLV)的潜在药理作用尚不清楚。在这项研究中,我们旨在研究PNS对脑膜淋巴系统和ICH的影响。进行了胶原酶-ICH模型以研究PNS的作用。行为测试,包括改良的神经系统严重程度评分(MNSS)和脚部故障测试以及血肿量来估计神经功能和治愈作用。通过免疫组织化学染色检测到MLV的结构和排水功能。对烧蚀MLV进行了Visudyne肠内麦格纳注射与红色激光光转化的结合。 RNA序列用于获得机械研究的mRNA谱。此外,PNS通过同时诱导淋巴管生成的同时促进了排水的过程。此外,通过光转化的Visudyne消融MLV显着阻止了PNS进行的改善神经缺陷的益处和血肿吸收。此外,RNA测序显示PNS依赖于完整的MLV调节轴突生成和炎症。其中,溶质载体家族17成员7(SLC17A7)和肿瘤坏死因子(TNF)被确定为靶基因的蛋白质 - 蛋白质相互作用网络的瓶颈和枢纽淋巴结,PNS可以通过增强淋巴管植物发生和促进性促进型促进型和促进性促进型ICH治疗,从而有效地治疗。首次研究了PN在MLV调控中的作用。这项研究为ICH医疗疗法中的PNS提供了一种新颖的见解。

Abstract

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.