基于NLRP3焦亡通路的中药干预溃疡性结肠炎的研究进展

Traditional Chinese Medicine Intervention in Ulcerative Colitis via NLRP3-Mediated Pyroptosis Pathway:A Review

溃疡性结肠炎(UC)主要发生于结直肠,该病病理机制复杂,与肠道的不可控性炎症反应密切相关。当前,西医主要使用糖皮质激素、免疫抑制剂等减轻肠道炎症,虽然可以在一定程度上阻遏UC的进展,但不良反应较大。越来越多研究证实,中医药防治UC具有明显的优势,可显著降低该病复发率。细胞焦亡是一种新型细胞死亡方式,可破坏细胞结构,释放胞内促炎物质,介导UC肠道免疫反应。研究人员认为中医药对细胞焦亡的干预主要表现为促进细胞焦亡(损其有余)和抑制细胞焦亡(补其不足),这与调节阴阳相一致。其中,中药主要通过抑制细胞焦亡(补其不足),减轻肠道免疫反应,起到治疗UC的作用。近年来,业界开展了大量研究探索中药通过调控NOD样受体热蛋白结构域相关蛋白3(NLRP3)焦亡通路治疗UC的作用机制,结果表明NLRP3焦亡通路是中药治疗UC的关键靶通路。但目前尚缺乏关于中药抑制NLRP3焦亡通路进而治疗UC的全面系统的总结。该文以“细胞焦亡”“NLRP3”“溃疡性结肠炎”及“中药”等为关键词,检索和分析近年来该领域中英文文献,发现调控NLRP3焦亡通路的中药主要包括清热燥湿类、调和气血类、行气通腑类和健脾祛湿类,这可为科研人员更为全面认识中医药对UC中NLRP3焦亡通路的机制提供帮助,以期为UC的治疗及进一步的药物开发提供理论依据。

Ulcerative colitis(UC)mainly occurs in the colon and rectum,with complex pathological mechanism.The occurrence of ulcerative colitis is associated with the uncontrollable inflammatory response of the intestine.The Western medicine therapy of UC mainly uses glucocorticoids and immunosuppressants to reduce intestinal inflammation.While blocking the progress of UC to a certain extent,it causes severe adverse reactions.More and more studies have confirmed that traditional Chinese medicine(TCM)has obvious advantages in the prevention and treatment of UC and can significantly reduce the recurrence of the disease.Pyroptosis,a novel form of cell death,can destroy cell structure,release intracellular pro-inflammatory substances,and mediate intestinal immune response in UC.TCM can promote pyroptosis(removing excess)or inhibit pyroptosis(replenishing deficiency),which is consistent with the regulation of Yin and Yang.TCM plays a role in the treatment of UC mainly by inhibiting pyroptosis(replenishing deficiency)and reducing intestinal immune response.In recent years,a large number of studies have been carried out to decipher the mechanism of TCM in the treatment of UC via NOD-like receptor protein domain 3(NLRP3)-mediated pyroptosis pathway.The results have demonstrated that NLRP3 pathway is the key target of TCM in the treatment of UC.However,a comprehensive summary remains to be carried out on the inhibition of NLRP3-mediated pyroptosis pathway by TCM in the treatment of UC.Therefore,we retrieved the articles in this field in recent years with the keywords"pyroptosis","NLRP3","ulcerative colitis",and"Chinese medicine".The Chinese medicines regulating NLRP3 pathway mainly have the functions of clearing heat and drying dampness,harmonizing Qi and blood,moving Qi and dredging fu-organs,and invigorating spleen and removing dampness.The findings can help researchers to fully understand the mechanism of TCM in the treatment of UC via the NLRP3 pathway and provide a theoretical basis for the treatment of UC and further drug development.