基于“阴火”理论探讨内皮细胞代谢重塑与肿瘤血管化关系及中医药干预思考

Relationship Between Metabolic Remodeling of Endothelial Cells and Tumor Angiogenesis Based on"Yin Fire"Theory and Intervention of Chinese Medicine

血管内壁的内皮细胞借助调节血管稳态、血管张力、细胞黏附、细胞增殖、凝血抗性、炎症因子等来响应机体的物理和化学信号,进而维持血管处于衡动稳定的状态。血管生成是肿瘤发生发展所需的关键条件,肿瘤血管化的病理模式为瘤体生长提供所需的营养和氧气,以促进其增殖。近年来,内皮细胞参与肿瘤血管渗入,驱动血管生成被认为是促进肿瘤转移的关键环节。血管内皮细胞可通过调控代谢重塑以满足肿瘤血管化过程中对物质和能量的需要,其异常的代谢特征使得其能更好地适应肿瘤微环境的变化,这种代谢的改变常被看作是肿瘤血管化进程的重要基础。中医“阴火”理论源自《黄帝内经》,原指“阴虚生内热”,属内伤之火范畴,后经历代医家推演变化,逐步形成“脾胃气虚-阴火上乘-气火失调”的病机认识。内皮细胞代谢重塑的发病过程是“阴火”病理表征的客观体现,而阴火造化生息、燔灼妄动之性又与肿瘤新生血管增生无制、亢变为害的疾病状态相吻合。脾胃亏虚与气机失衡的改变可致水谷精微不得布散,发生代谢障碍,停久为痰为瘀,与血脉相搏结,致使局部环境异化(肿瘤微环境形成)、脉道不利(内皮细胞代谢失衡),异变形成肿瘤新生血管。在“阴火”证候要素指导下,围绕气与火的相关性,运用“扶正调气”的治法遣方用药,可调节内皮细胞代谢功能,达到机体相对平衡状态,进而抑制肿瘤血管新生。基于以上认识,该文围绕内皮细胞代谢重塑与阴火相关理论,阐发学术微旨,以期为中医药干预肿瘤血管化进程提供一定的理论支持。

Endothelial cells in the inner wall of blood vessels respond to physical and chemical signals of the body by regulating vascular homeostasis,vascular tension,cell adhesion,cell proliferation,coagulation resistance and inflammatory factors,to maintain the stability of blood vessels.Angiogenesis is the key condition for tumor evolution,and the pathological mode of tumor angiogenesis provides nutrients and oxygen for tumor growth and promotes its proliferation.In recent years,endothelial cells have participated in tumor vascular infiltration and driven angiogenesis,which is considered to be the point link in tumor metastasis.By regulating metabolic remodeling,vascular endothelial cells provide the materials and energy needed in the process of tumor angiogenesis,and their abnormal metabolic characteristics facilitate their adaption to the changes of tumor microenvironment,which is often regarded as an important basis for tumor angiogenesis.The''Yin fire''theory in traditional Chinese medicine,originating from Huangdi's Internal Classic(Huang Di Nei Jing),originally meant Yin deficiency generates internal heat,and belonged to the category of fire of internal injury.After the deduction and changes by physicians over the ages,the pathogenesis of''spleen and stomach Qi deficiency-Yin fire rising-Qi and fire disharmony''was gradually formed.The pathogenesis of metabolic remodeling of endothelial cells manifests the pathological characterization of Yin fire in an objective way,which is consistent with the disease state of uncontrolled and hyperactive tumor neovascularization.Changes in spleen and stomach Qi deficiency as well as imbalance of Qi movement lead to the failure of water and food in distribution,and thus metabolic disorders occur.Long term retention turns in phlegm and blood stasis,which combat with blood vessels,and result in abnormal local environment(formation of tumor microenvironment),adverse pulse channel(imbalance of endothelial cell metabolism),and tumor neovascularization.Under the guidance of''Yin fire''syndrome elements and by focusing on the correlation between Qi and fire,prescriptions are made based on the treatment method of''strengthening the body and regulating Qi''to regulate the metabolic function of endothelial cells,thus achieving a relatively balanced state of the body and inhibiting tumor angiogenesis.As a result,this study,centering on the metabolic remodeling of endothelial cells and''Yin fire''theory,elucidated the academic ideas,with the purpose of providing some theoretical support for the intervention of tumor vascularization by Chinese medicine.