中医药调控MAPK经典信号通路辨治银屑病研究进展

Research Progress of Regulating MAPK Classical Signal Pathway of Traditional Chinese Medicine in Treating Psoriasis

银屑病发病机制复杂,涉及多基因、多细胞、多分子,通过级联反应将信号进行逐层传递,从而形成与疾病相关的多种生物学通路,对于银屑病相关信号通路的研究已经成为探索疾病发病机制和药物干预的核心方式。丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)信号通路是真核生物信号传递网络中的重要途径之一,是细胞增殖、分化、细胞凋亡及应激反应的关键信号通路,参与疾病炎症反应、免疫调控等环节。在银屑病患者皮损中,MAPK及其亚族ERK、p38、JNK和BMK1的生物活性及表达水平升高,将MAPK信号通路作为切入点和突破口,有助于重新梳理和发现银屑病微观机制的上下游相关靶点调控方式,不断延伸对银屑病机制的探索。近年来,中医药界开展了大量研究,探索中医药通过调控MAPK通路治疗银屑病的机制,结果表明MAPK通路是中医药治疗银屑病的关键靶通路。该文通过对具有消、清、补功效的中药复方制剂及丹皮酚、紫草素、靛蓝、白鲜碱、苦参碱、芳姜黄酮、雷公藤多苷、羟基红花黄色素A等中药有效成分参与下的MAPK信号通路的靶位进行研究,整合不同细胞因子如白细胞介素(IL)-6、IL-17、IL-22、IL-23、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ等作用于多种MAPK信号通路家族亚型的分子机制,以期为银屑病的治疗以及进一步的药物开发提供理论依据。

The pathogenesis of psoriasis is complex,involving multi-genes,multi-cells,multi-molecules.Through cascade reaction,signals are transmitted layer by layer,thus forming a variety of biological pathways related to the disease.The research on psoriasis-related signal pathways has become the core way to explore the pathogenesis of the disease and drug intervention.Mitogen-activated protein kinases(MAPK)signaling pathway is one of the important pathways in the eukaryotic signal transmission network.It is the key signaling pathway of cell proliferation,differentiation,apoptosis and stress response,and participates in the inflammatory response and immune regulation of diseases.In the skin lesions of patients with psoriasis,the biological activity and expression level of MAPK and its subfamilies ERK,p38,JNK and BMK1 are increased.Taking MAPK signaling pathway as the breakthrough point is helpful to reorganize and discover the upstream and downstream related target regulation modes of psoriasis micro-mechanism,and continuously extend the exploration of psoriasis mechanism.In recent years,a great deal of research has been carried out in the field of traditional Chinese medicine to explore the mechanism of TCM treating psoriasis by regulating MAPK pathway.The results show that MAPK pathway is the key target pathway of TCM treating psoriasis.In this paper,the target of MAPK signal pathway with the participation of Chinese herbal compound preparation with the effects of eliminating,clearing and nourishing,paeonol,shikonin,indigo,dictamnine,matrine,aromatic ginger flavone,tripterygium wilfordi polyglycoside,hydroxysafflor yellow A,etc.was studied.To integrate the molecular mechanism of different cytokines,such as interleukin(IL)-6,IL-17,IL-22,IL-23,tumor necrosis factor(TNF)-α,interferon(IFN)-,etc.,acting on various MAPK signal pathway family subtypes,so as to provide theoretical basis for the treatment of psoriasis and further drug development.