从Ras / MEK / ERK和PI3K/ Akt / eNOS信号通路研究培元化瘀方对慢性硬膜下血肿的干预机制

The postoperative recurrence of chronic subdural hematoma (CSDH) is a very troublesome clinical problem, and adventitia microangiogenesis of hematoma is an important cause of this recurrence. Under the guidance of Professor Zhang Xuewen, the national master of TCM, our team formed the remedy of Peiyuan Huayu Decoction to treat CSDH, which was clinically proven to promote the absorption of hematoma, improve neurological function and reduce recurrence. Experiments have confirmed that this prescription can inhibit the expression of VEGF in the outer membrane of hematoma and minimize the hypergenesis of microvessels. Based on this, the scientific hypothesis is that Peiyuan Huayu Decoction can prevent the recurrence of CSDH by blocking the signaling pathways of Ras / MEK / ERK and PI3K / Akt / eNOS to inhibit the induction of angiogenesis by VEGF.Guiding by TCM theory, and taking the absorption and recurrence of postoperative hematomas in patients with CSDH, the expression of VEGF-related factors in animal models, and changes in the correlation factors of Ras / MEK / ERK and PI3K / Akt / eNOS signaling pathways in vitro as observation points, this project intends to have an in-depth study of the regulation targets of the Peiyuan Huayu Decoction on microangiogenesis and analyze the intervention mechanism of CSDH to provide experimental basis for Chinese medicine treatment of CSDH by using the techniques of functional magnetic resonance imaging (FMRI), cell culture in vitro and molecular biology.

慢性硬膜下血肿（CSDH）术后复发是临床非常棘手的问题，血肿外膜微血管新生是引起复发的重要事件。本团队在国医大师张学文教授的指导下，形成培元化瘀方治疗CSDH，临床证实，本方能促进血肿吸收和神经功能改善、减少复发；实验证实，本方能抑制血肿外膜VEGF表达，减轻微血管的过度新生。据此提出科学假说：培元化瘀方能通过阻滞Ras / MEK / ERK和PI3K/ Akt / eNOS信号通路、抑制VEGF对血管生成的诱导，阻止CSDH复发。本项目拟在中医理论指导下，运用功能磁共振成像技术、体外细胞培养技术、分子生物学技术，以CSDH患者术后血肿的吸收和复发、动物模型中对VEGF相关因子的表达、体外培养Ras / MEK / ERK和PI3K/ Akt / eNOS信号通路相关因子的变化为观察点，深入研究培元化瘀方对微血管新生的调控靶点，探析对CSDH的干预机制，为中医治疗CSDH提供实验依据。

本项目研究通过临床研究、在体实验、离体实验等多个方面，系统的进行了培元化瘀方治疗CSDH的作用机制研究。研究证实，培元化瘀方对CSDH具有明确的治疗作用，特别是降低复发率具有显著的优势。这一作用是通过Ras/MEK/ERK和PI3K/Akt/eNOS信号通路的调控，抑制血肿外膜微血管新生，从而阻滞“CSDH循环”实现的。研究完成了既定内容，实现了预期目标。研究过程中，项目组对目前CSDH国内外治疗现状和治疗方法进行了系统性分析和回顾，为临床治疗提供了重要的参考依据。研究过程中发现，CSDH发病的必要因素不是创伤而是衰老，导致这一过程的原因可能与血管老化引起的血管通透性的改变和结构的破坏具有一定的关系。这一发现一定程度上解释了为什么CSDH只在老年人发病的现象，将为CSDH的病因学研究和治疗新药的研发提供重要的线索。这也是项目组后期继续深入研究的方向。