核受体PPARγ在溃疡性结肠炎中的作用及中医药干预研究进展

Role of PPARγin Ulcerative Colitis and Traditional Chinese Medicine Intervention:A Review

溃疡性结肠炎(UC)是一种主要累及结肠和直肠的慢性炎症性肠病,以腹痛、血性腹泻和里急后重感为典型症状,病理机制尚未完全阐明。该病反复发作,严重影响患者生活质量,而常用的治疗药物具有临床疗效欠佳、疗程长、不良反应多等局限,故亟需寻找新的治疗药物。过氧化物酶体增殖物激活受体γ(PPARγ)是一种配体依赖性核受体蛋白,在维持肠道稳态中发挥了重要作用,并与UC的发生发展密切相关。中医药治疗UC具有多靶点、不良反应小等优势,近年大量研究发现中医药可以通过调控核受体PPARγ发挥治疗UC的作用。结果表明PPARγ是中医药治疗UC的重要靶点,中医药多采用清热燥湿、行气活血化瘀、健脾温肾和攻补兼施之法干预PPARγ,一方面直接激活PPARγ,或通过介导核转录因子-κB(NF-κB)、丝裂原活化蛋白激酶(MAPK)、Toll样受体4(TLR4)等信号通路、调节辅助性T细胞17(Th17)/调节性T细胞(Treg)平衡、促进巨噬细胞由促炎M1型向抗炎M2型极化等方式控制促炎因子与抗炎因子水平,从而抑制肠道炎症反应;另一方面通过调节肠道代谢,激活PPARγ,降低硝酸盐水平并维持局部缺氧状态,从而调节专性厌氧菌与兼性厌氧菌平衡,改善肠道微生态,最终起到防治UC的作用。该文将核受体PPARγ在UC中的作用及近5年中医药通过干预PPARγ治疗UC的研究进展进行梳理和总结,旨在为UC的治疗及新药研发提供思路。

Ulcerative colitis(UC)is a chronic inflammatory bowel disease primarily affecting the colon and rectum,with the typical symptoms such as abdominal pain,bloody diarrhea,and tenesmus.The pathogenesis of UC remains to be fully elucidated.The disease is prone to recurrence,seriously affecting the patients'quality of life.Conventional therapies for UC have limitations,including unsatisfactory clinical efficacy,lengthy courses,and adverse reactions.Therefore,there is an urgent need to explore new therapeutic agents.Peroxisome proliferator-activated receptor gamma(PPARγ),a ligand-dependent nuclear receptor protein that plays a crucial role in maintaining intestinal homeostasis,is closely associated with the onset and development of UC.Traditional Chinese medicine(TCM)has advantages such as multi-targeting and mild side effects in the treatment of UC.Recent studies have shown that TCM can exert the therapeutic effects on UC by modulating PPARγ.The TCM methods for regulating PPARγinclude clearing heat,drying dampness,moving Qi,activating blood,resolving stasis,invigorating the spleen,warming the kidney,and treating with both tonification and elimination.On one hand,TCM directly activates PPARγor mediates signaling pathways such as nuclear factor-κB(NF-κB),mitogen-activated protein kinase(MAPK),Tolllike receptor 4(TLR4),and regulates helper T cell 17(Th17)/regulatory T cell(Treg)balance to promote macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,thereby inhibiting intestinal inflammation.On the other hand,TCM regulates the intestinal metabolism to activate PPARγ,lower the nitrate level,and maintain local hypoxia.In this way,it can restore the balance between specialized anaerobes and facultative anaerobes,thereby improving the gut microbiota and treating UC.This article summarizes the role of PPARγin UC and reviews the research progress of TCM in treating UC by intervening in PPARγin the last five years,aiming to give insights into the treatment and new drug development for UC.