基于JAK/STAT信号通路的中药治疗慢性萎缩性胃炎药理机制研究进展

Advances in pharmacological mechanism of JAK/STAT signaling pathway-based traditional Chinese medicine for the treatment of chronic atrophic gastritis

现关于中医药干预慢性萎缩性胃炎(chronic atrophic gastritis,CAG)的临床研究和基础实验研究已成为消化系统疾病中的研究热点。Janus蛋白酪氨酸激酶(Janus protein tyrosine kinase,JAK)/信号转导子与激活子(signal transducer and activator of transcription,STAT)信号通路的状态与消化道疾病的发生与进展十分密切。诸多研究表明中药可通过多种机制调控该信号通路干预CAG的进展,大致可分为以下几个方面:通过抑制JAK2/STAT3、核转录因子-κB/STAT1通路激活或促使白介素-4(interleukin-4,IL-4)/STAT6激活达到干预CAG的目的;同时降低IL-6、IL-1β等相关炎症因子表达,不仅可抑制相关通路激活,亦可起到减轻胃黏膜炎症的作用;再者上调抑癌基因p21、下调原癌基因表达防止受损的胃黏膜进一步恶化;最后还可调节生存素、B淋巴细胞瘤2家族调控细胞凋亡/增殖平衡机制逆转胃黏膜萎缩及肠化生。

Clinical and basic experimental studies on traditional Chinese medicine(TCM)intervention in chronic atrophic gastritis(CAG)have now become a research hotspot in digestive diseases.The state of janus protein tyrosine kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway is closely related to the occurrence and progression of digestive diseases.Many studies have shown that TCM can intervene in the progression of CAG by regulating this signaling pathway through a variety of mechanisms,which can be broadly categorized into the following aspects:on the one hand,by inhibiting the activation of JAK2/STAT3,NF-κB/STAT1 pathway can promote the activation of interleukin-4(IL-4)/STAT6 to intervene in CAG;at the same time,TCM can decrease the expression of relevant inflammatory factors,such as IL-6,IL-1β,not only inhibit the activation of the relevant pathway,but also play a role in reducing the inflammation of the gastric mucosa;in addition to up-regulating the oncogene p21,down-regulating the expression of the proto-oncogene cancer-Myc(c-Myc)to prevent the further deterioration of the damaged gastric mucosa;and finally,also can regulate the Survivin and b-cell lymphoma-2(Bcl-2)family of regulatory mechanisms of apoptosis/proliferative balance of the gastric mucosa and intestinal chemotaxis reversed.