浏览全部资源
扫码关注微信
成都中医药大学 附属医院,成都 610072
王颖逸,在读硕士,从事中医脾胃病的防治和研究,E-mail:616956551@qq.com
张怡,教授,硕士生导师,从事中医脾胃系疾病的防治与研究,E-mail:zhangyi2288@163.com
收稿日期:2022-10-25,
网络出版日期:2023-02-13,
纸质出版日期:2023-08-05
移动端阅览
王颖逸,刘青松,张怡等.基于NLRP3炎性小体探讨中医药治疗溃疡性结肠炎的研究进展[J].中国实验方剂学杂志,2023,29(15):232-241.
WANG Yingyi,LIU Qingsong,ZHANG Yi,et al.Traditional Chinese Medicine in Treatment of Ulcerative Colitis Based on NLRP3 Inflammasome: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(15):232-241.
王颖逸,刘青松,张怡等.基于NLRP3炎性小体探讨中医药治疗溃疡性结肠炎的研究进展[J].中国实验方剂学杂志,2023,29(15):232-241. DOI: 10.13422/j.cnki.syfjx.20230502.
WANG Yingyi,LIU Qingsong,ZHANG Yi,et al.Traditional Chinese Medicine in Treatment of Ulcerative Colitis Based on NLRP3 Inflammasome: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(15):232-241. DOI: 10.13422/j.cnki.syfjx.20230502.
溃疡性结肠炎(UC)是临床上常见的一种炎症性肠病(IBD),临床表现为腹痛、腹泻、黏液脓血便,有难治愈、复发率高等特点。UC发病机制与异常免疫反应、肠道组织氧化应激、炎症反应等有关。研究表明,NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体的异常激活参与UC的病理进程,激活了肠上皮细胞中氧化、焦亡、炎症等病理机制,因此阻断NLRP3的异常激活有利于缓解UC。目前UC的西医治疗以水杨酸类、糖皮质激素、生物制剂为主,但总体疗效不佳。中医药治疗本病具有疗效显著、复发率低的优势。近年来,运用中医药方法治疗UC的基础研究已取得显著进展,研究发现通过中药干预NLRP3炎性小体可以明显促进肠黏膜愈合,治疗UC,其作用机制涉及到多靶点、多层次、多通路。该文就近年来中医药靶向调控NLRP3炎性小体对UC影响的实验研究进行总结,发现NLRP3与胱天蛋白酶-1(Caspase-1)、核转录因子-
κ
B(NF-
κ
B)等因子相互作用从而促进了肠上皮细胞中促炎因子的释放及细胞焦亡,激活了氧化应激、炎症反应等病理机制,中医药作用于NLRP3炎性小体及其上下游因子阻断UC的病理进程,抑制肠黏膜的病理损伤进而缓解结肠溃疡。以期为UC的防治及进一步的药物开发提供理论依据。
Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD) in clinical practice, characterized by symptoms such as abdominal pain, diarrhea, and bloody mucus in the stool. It is difficult to cure and has a high recurrence rate. The pathogenesis of UC is related to abnormal immune response, oxidative stress in intestinal tissues, and inflammatory reactions. As reported, the abnormal activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is involved in the pathological process of UC. This activation triggers pathological mechanisms such as oxidative stress, pyroptosis, and inflammation in intestinal epithelial cells. Therefore, blocking the abnormal activation of NLRP3 is beneficial for alleviating UC. Currently, western medicine treatment for UC mainly includes salicylic acid derivatives, corticosteroids, and biologics, but the overall efficacy is unsatisfactory. Traditional Chinese medicine (TCM) treatment of this disease has the advantages of significant efficacy and low recurrence rate. In recent years, great advances have been made in the basic research of using TCM methods to treat UC. Studies have found that TCM intervention targeting the NLRP3 inflammasome can significantly promote intestinal mucosal healing and treat UC, and the mechanism of action involves multiple targets, levels, and pathways. This article summarized the experimental research on the impact of TCM targeting the NLRP3 inflammasome on UC in recent years, and found that NLRP3 interacted with factors such as Caspase-1 and nuclear factor-
κ
B (NF-
κ
B), thereby promoting the release of pro-inflammatory factors and cell pyroptosis in intestinal epithelial cells. This activation triggered oxidative stress, inflammatory reactions, and other pathological mechanisms. TCM acted on the NLRP3 inflammasome and its upstream and downstream factors to block the pathological process of UC, inhibit the pathological damage to the intestinal mucosa, and thereby alleviate colonic ulcers. The findings of this study provide a theoretical basis for the prevention and treatment of UC and further drug development.
张娇娇 , 张帆 , 余星星 , 等 . 溃疡性结肠炎发病机制及中西医治疗研究进展 [J]. 辽宁中医药大学学报 , 2021 , 23 ( 1 ): 70 - 74 .
张海明 , 梁凤霞 , 杨胜兰 , 等 . 基于NLRP3炎症小体探讨中医药防治溃疡性结肠炎的机制 [J]. 中国中西医结合消化杂志 , 2021 , 29 ( 7 ): 524 - 528 .
郭帆 , 吴东南 , 刘玲 , 等 . 酸枣仁汤防治睡眠剥夺性大鼠学习记忆功能变化及其对NLRP3通路的影响 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 2 ): 22 - 27 .
金晓敏 , 张晓熙 , 郭璐 , 等 . 基于NLRP3炎性体轴土茯苓总黄酮对痛风性关节炎的作用和机制 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 4 ): 90 - 95 .
郑一 , 郭鹤 , 包永睿 , 等 . 基于NF- κ B/NLRP3/Caspase-1通路介导的巨噬细胞焦亡探究葛根芩连汤对AS易损斑块的干预机制 [J]. 中国实验方剂学杂志 , 2022 , 28 ( 11 ): 70 - 78 .
肖懿 , 冯志乔 , 张桂贤 , 等 . 血必净注射液调节线粒体N-甲酰肽/NLRP3炎症通路对重症急性胰腺炎大鼠模型的治疗机制 [J]. 中国实验方剂学杂志 , 2022 , 28 ( 7 ): 88 - 94 .
GAO L , CHONG E , PENDHARKAR S , et al . The effects of NLRP3 inflammasome inhibition in experimental acute pancreatitis:A systematic review and meta-analysis [J]. Pancreas , 2022 , 51 ( 1 ): 13 - 24 .
RANSON N , VELDHUIS M , MITCHELL B , et al . NLRP3-dependent and -independent processing of interleukin (il)-1beta in active ulcerative colitis [J]. Int J Mol Sci , 2018 , 20 ( 1 ).
BIAN Z , QIN Y , LI L , et al . Schisandra chinensis (Turcz.) Baill. protects against DSS-induced colitis in mice: Involvement of TLR4/NF- κ B/NLRP3 inflammasome pathway and gut microbiota [J]. J Ethnopharmacol , 2022 , 298 : 115570 .
谢晶日 , 孙涛 , 张冰 . 溃疡性结肠炎的中医药治疗进展及相关优势探讨 [J]. 辽宁中医杂志 , 2016 , 43 ( 2 ): 425 - 427 .
MARTINON F , BURNS K , TSCHOPP J . The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta [J]. Mol Cell , 2002 , 10 ( 2 ): 417 - 426 .
BLEVINS H M , XU Y , BIBY S , et al . The NLRP3 inflammasome pathway: A review of mechanisms and inhibitors for the treatment of inflammatory diseases [J]. Front Aging Neurosci , 2022 , 14 : 879021 .
SARBADHIKARY P , GEORGE B P , ABRAHAMSE H . Inhibitory role of berberine,an isoquinoline alkaloid,on NLRP3 inflammasome activation for the treatment of inflammatory diseases [J]. Molecules , 2021 , 26 ( 20 ): 6238 .
MATHUR A , HAYWARD J A , MAN S M . Molecular mechanisms of inflammasome signaling [J]. J Leukoc Biol , 2018 , 103 ( 2 ): 233 - 257 .
GONG Z , ZHAO S , ZHOU J , et al . Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1 β production [J]. Mol Immunol , 2018 , 104 : 11 - 19 .
ZHEN Y , ZHANG H . NLRP3 inflammasome and inflammatory bowel disease [J]. Front Immunol , 2019 , 10 : 276 .
章康 , 赵婷 , 夏丹 , 等 . 白头翁汤正丁醇提取物通过下调NLRP3炎症小体及相关信号通路治疗小鼠外阴阴道念珠菌病的作用机制研究 [J]. 中国中药杂志 , 2022 , 47 ( 9 ): 2516 - 2524 .
刘雯 , 郭文洁 , 徐强 , 等 . NLRP3炎症小体调控机制研究进展 [J]. 药学学报 , 2016 , 51 ( 10 ): 1505 - 1512 .
魏红霞 . ATP通过调节AMPK信号诱导巨噬细胞炎症小体活化和细胞焦亡 [D]. 广州 : 暨南大学 , 2017 .
KAMARI Y , WERMAN-VENKERT R , SHAISH A , et al . Differential role and tissue specificity of interleukin-1alpha gene expression in atherogenesis and lipid metabolism [J]. Atherosclerosis , 2007 , 195 ( 1 ): 31 - 38 .
LATZ E , XIAO T S , STUTZ A . Activation and regulation of the inflammasomes [J]. Nat Rev Immunol , 2013 , 13 ( 6 ): 397 - 411 .
冯皓月 , 丁蕊 , 周琦 , 等 . 及中医药防治的研究进展NLRP3炎症小体在糖尿病神经病变中的作用 [J]. 中国中药杂志 , 2023 , 48 ( 2 ): 300 - 310 .
LIU C , ZENG Y , WEN Y , et al . Natural products modulate cell apoptosis: A promising way for the treatment of ulcerative colitis [J]. Front Pharmacol , 2022 , 13 : 806148 .
MAURO A G , BONAVENTURA A , MEZZAROMA E , et al . NLRP3 inflammasome in acute myocardial infarction [J]. J Cardiovasc Pharmacol , 2019 , 74 ( 3 ): 175 - 187 .
李秋月 , 许海玉 , 杨洪军 . 促炎因子TNF- α ,IL-1 β ,IL-6在神经病理性疼痛中的研究进展 [J]. 中国中药杂志 , 2017 , 42 ( 19 ): 3709 - 3712 .
杨连雷 , 陈梦娜 , 李善高 , 等 . NOD样受体蛋白3炎症小体表达水平与溃疡性结肠炎病变活动的关系 [J]. 中华消化杂志 , 2019 , 39 ( 4 ): 229 - 236 .
UNGARO R , MEHANDRU S , ALLEN P B , et al . Ulcerative colitis [J]. Lancet , 2017 , 389 ( 10080 ): 1756 - 1770 .
TOURKOCHRISTOU E , AGGELETOPOULOU I , KONSTANTAKIS C , et al . Role of NLRP3 inflammasome in inflammatory bowel diseases [J]. World J Gastroenterol , 2019 , 25 ( 33 ): 4796 - 4804 .
RANSON N , VELDHUIS M , MITCHELL B , et al . NLRP3-dependent and -independent processing of interleukin (il)-1beta in active ulcerative colitis [J]. Int J Mol Sci , 2018 , 20 ( 1 ).
唐立 , 陆岩 , 欧阳满照 . 细胞焦亡与溃疡性结肠炎研究的最新进展 [J]. 广东医学 , 2021 , 42 ( 11 ): 1393 - 1399 .
JIE F , XIAO S , QIAO Y , et al . Kuijieling decoction suppresses NLRP3-mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro [J]. J Ethnopharmacol , 2021 , 264 : 113243 .
吴娜 , 万治平 , 韩玲 , 等 . 黄芩汤对溃疡性结肠炎小鼠NLRP3/Caspase-1细胞焦亡通路的影响 [J]. 中国中药杂志 , 2021 , 46 ( 5 ): 1191 - 1196 .
CHEN X , LIU G , YUAN Y , et al . NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF- κ B signaling [J]. Cell Death Dis , 2019 , 10 ( 12 ): 906 .
PERERA A P , FERNANDO R , SHINDE T , et al . MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice [J]. Sci Rep , 2018 , 8 ( 1 ): 8618 .
NEUDECKER V , HANEKLAUS M , JENSEN O , et al . Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome [J]. J Exp Med , 2017 , 214 ( 6 ): 1737 - 1752 .
ZOHNY M H , ALROUJI M , ALHAJLAH S , et al . Diacetylrhein, an anthraquinone antiarthritic agent, suppresses dextran sodium sulfate-induced inflammation in rats: A possible mechanism for a protective effect against ulcerative colitis [J]. Biomed Pharmacother , 2022 , 154 : 113651 .
汪青楠 , 李娟梅 , 倪瑶 , 等 . 中医治疗溃疡性结肠炎的研究进展 [J]. 吉林中医药 , 2019 , 39 ( 9 ): 1251 - 1255 .
张声生 , 沈洪 , 郑凯 , 等 . 溃疡性结肠炎中医诊疗专家共识意见(2017) [J]. 中华中医药杂志 , 2017 , 32 ( 8 ): 3585 - 3589 .
吴娜 , 毛祥坤 , 于男 , 等 . 细胞焦亡与溃疡性结肠炎及中医药调控的研究进展 [J]. 中国实验方剂学杂志 , 2020 , 26 ( 15 ): 200 - 206 .
郑娟红 , 陈怡 . 重症溃疡性结肠炎患者血清NOD样受体蛋白3、半胱氨酸天冬氨酸特异性蛋白酶1和核因子 κ B mRNA表达水平及临床意义 [J]. 中华危重症医学杂志:电子版 , 2019 , 12 ( 1 ): 31 - 36 .
岳备 . 乔松素减轻小鼠溃疡性结肠炎作用机制研究 [D]. 上海 : 上海中医药大学 , 2019 .
XIE J , LIU L , LI H , et al . Ink melanin from Sepiapharaonis ameliorates colitis in mice via reducing oxidative stress, andprotecting the intestinal mucosal barrier [J]. Food Res Int , 2022 , 151 : 110888 .
MAHMOUD T N , EL-MAADAWY W H , KANDIL Z A , et al . Canna x generalis L.H. Bailey rhizome extract ameliorates dextran sulfate sodium-induced colitis via modulating intestinal mucosal dysfunction, oxidative stress, inflammation, and TLR4/NF- κ B and NLRP3 inflammasome pathways [J]. J Ethnopharmacol , 2021 , 269 : 113670 .
ZHANG Q , WANG S , JI S . Trifolirhizin regulates the balance of Th17/Treg cells and inflammation in the ulcerative colitis mice through inhibiting the TXNIP-mediated activation of NLRP3 inflammasome [J]. Clin Exp Pharmacol Physiol , 2022 , 49 ( 8 ): 787 - 796 .
LIU Q , ZUO R , WANG K , et al . Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF- κ B pathway [J]. Acta Pharmacol Sin , 2020 , 41 ( 6 ): 771 - 781 .
YU S , QIAN H , ZHANG D , et al . Ferulic acid relieved ulcerative colitis by inhibiting the TXNIP/NLRP3 pathway in rats [J]. Cell Biol Int , 2023 , 47 ( 2 ): 417 - 427 .
HUANG S , TAO R , ZHOU J , et al . Trans-10-hydroxy-2-decenoic acid alleviates dextran sulfate sodium-induced colitis in mice via regulating the inflammasome-mediated pyroptotic pathway and enhancing colonic barrier function [J]. Mol Nutr Food Res , 2022 , 66 ( 12 ): e2100821 .
郑健豪 , 钟继红 , 曹海军 , 等 . 雷公藤多苷通过NOXs-ROS-NLRP3炎症小体信号通路抑制结肠炎症 [J]. 中国病理生理杂志 , 2016 , 32 ( 9 ): 1653 - 1659 .
SALAMA R M , DARWISH S F , EL SHAFFEI I , et al . Morus macroura Miq. fruit extract protects against acetic acid-induced ulcerative colitis in rats: Novel mechanistic insights on its impact on miRNA-223 and on the TNF- α /NF- κ B/NLRP3 inflammatory axis [J]. Food Chem Toxicol , 2022 , 165 : 113146 .
YAO H , YAN J , YIN L , et al . Picroside Ⅱ alleviates DSS-induced ulcerative colitis by suppressing the production of NLRP3 inflammasomes through NF- κ B signaling pathway [J]. Immunopharmacol Immunotoxicol , 2022 , 44 ( 3 ): 437 - 446 .
刘琦 , 罗霞 , 罗爽 , 等 . 芍药苷通过抑制NLRP3炎症小体治疗溃疡性结肠炎小鼠的研究 [J]. 中药新药与临床药理 , 2018 , 29 ( 4 ): 409 - 414 .
WU B , ZHOU Q , HE Z , et al . Protective effect of the abelmoschus manihot flower extract on DSS-induced ulcerative colitis in mice [J]. Evid Based Complement Alternat Med , 2021 , 2021 : 7422792 .
PAN X , WANG H , ZHENG Z , et al . Pectic polysaccharide from Smilax china L. ameliorated ulcerative colitis by inhibiting the galectin-3/NLRP3 inflammasome pathway [J]. Carbohydr Polym , 2022 , 277 : 118864 .
LV Q , XING Y , LIU J , et al . Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation [J]. Acta Pharm Sin B , 2021 , 11 ( 9 ): 2880 - 2899 .
李时超 , 殷佩浩 , 陈腾 , 等 . 华蟾素对溃疡性结肠炎大鼠的作用及机制 [J]. 中国临床药理学杂志 , 2021 , 37 ( 21 ): 2924 - 2928 .
YAO X , ZHANG C , XING Y , et al . Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis [J]. Nat Commun , 2017 , 8 ( 1 ): 1896 .
WANG K , LV Q , MIAO Y M , et al . Cardamonin, a natural flavone, alleviates inflammatory bowel disease by the inhibition of NLRP3 inflammasome activation via an AhR/Nrf2/NQO1 pathway [J]. Biochem Pharmacol , 2018 , 155 : 494 - 509 .
CHAO L , LIN J , ZHOU J , et al . Polyphenol rich forsythia suspensa extract alleviates DSS-induced ulcerative colitis in mice through the Nrf2-NLRP3 pathway [J]. Antioxidants (Basel) , 2022 , 11 ( 3 ): 127 .
MARINHO S , ILLANES M , AVILA-ROMAN J , et al . Anti-Inflammatory effects of rosmarinic acid-loaded nanovesicles in acute colitis through modulation of NLRP3 inflammasome [J]. Biomolecules , 2021 , 11 ( 2 ): 162 .
ZHANG W , WANG W , SHEN C , et al . Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome [J]. Aging (Albany NY) , 2021 , 13 ( 19 ): 23193 - 23209 .
TIAN M , MA P , ZHANG Y , et al . Ginsenoside Rk3 alleviated DSS-induced ulcerative colitis by protecting colon barrier and inhibiting NLRP3 inflammasome pathway [J]. Int Immunopharmacol , 2020 , 85 : 106645 .
王德龙 , 卢爱妮 , 郑红斌 , 等 . 芍药汤调控TXNIP/NLRP3通路改善溃疡性结肠炎的作用机制 [J]. 中华中医药杂志 , 2021 , 36 ( 6 ): 3240 - 3245 .
MA K L , HAN Z J , SUN J , et al . Mechanism of Sanhuang Decoction in alleviating dextran sulfate sodium induced ulcerative colitis in mice with Candida albicans colonization:Based on high-throughput transcriptome sequencing [J]. Chin J Chin Mater Med , 2021 , 46 ( 15 ): 3915 - 3925 .
张嘉骏 , 施家希 , 黄娟 , 等 . 参苓白术散对溃疡性结肠炎小鼠NLPR3,NLPR6蛋白及相关炎症因子表达的影响 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 4 ): 36 - 41 .
YAN S , WANG P , WEI H , et al . Treatment of ulcerative colitis with Wu-Mei-Wan by inhibiting intestinal inflammatory response and repairing damaged intestinal mucosa [J]. Phytomedicine , 2022 , 105 : 154362 .
YE B , LAI L . Yu Shi An Chang Fang ameliorates TNBS-induced colitis in mice by reducing inflammatory response and protecting the intestinal mucosal barrier [J]. Evid Based Complement Alternat Med , 2021 , 2021 : 8870901 .
YU W , LIANG Z , LI Q , et al . The pharmacological validation of the Xiao-Jian-Zhong formula against ulcerative colitis by network pharmacology integrated with metabolomics [J]. J Ethnopharmacol , 2022 , 298 : 115647 .
曾于恒 , 杨芳 , 何永恒 . 白芍七物颗粒对NLRP3炎症体介导溃疡性结肠炎调控研究 [J]. 时珍国医国药 , 2019 , 30 ( 04 ): 782 - 785 .
XUE S , XUE Y , DOU D , et al . Kui Jie Tong ameliorates ulcerative colitis by regulating gut microbiota and NLRP3/Caspase-1 classical pyroptosis signaling pathway [J]. Dis Markers , 2022 , 2022 : 2782112 .
夏子健 , 李亚桐 , 刘晓露 , 等 . 槐绛方调控NLRP3/Caspase-1通路抗溃疡性结肠炎损伤的机制研究 [J]. 中草药 , 2021 , 52 ( 23 ): 7221 - 7228 .
ZAKI M H , BOYD K L , VOGEL P , et al . The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis [J]. Immunity , 2010 , 32 ( 3 ): 379 - 391 .
陈双兰 , 刘青松 , 张怡 , 等 . 基于细胞信号通路探讨中药复方治疗溃疡性结肠炎的研究进展 [J]. 中华中医药学刊 , 2023 , 41 ( 1 ): 115 - 119 .
0
浏览量
34
下载量
1
CSCD
关联资源
相关文章
相关作者
相关机构