基于NF-κB信号通路的益生菌治疗溃疡性结肠炎的研究进展
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摘要
溃疡性结肠炎(UC)是一种肠道非特异性炎症性疾病,迁延不愈,严重影响患者的生活质量。目前认为,肠道菌群的改变是诱发和维持结肠炎症的主要原因。临床上应用益生菌制剂作为UC患者的辅助治疗,可平衡患者肠道菌群,减轻炎症反应。UC患者免疫调节功能紊乱,TLR4及其信号传导通路是UC发病的重要环节。易感人群肠道中的菌群突破肠上皮屏障,免疫系统被各种微生物抗原激活,炎症细胞活化从而导致结肠黏膜组织产生炎症反应,该过程可由TLR4-NF-κB信号传导通路介导。本研究就益生菌基于TLR4-NF-κB信号通路对溃疡性结肠炎的治疗进行综述。
Ulcerative colitis(UC)is a kind of nonspecific inflammatory diseases in the intestine,which is refractory and seriously affects the quality of life of patients.It is believed that the changes of intestinal flora are the main factors inducing and maintaining colonic inflammation.The clinical application of probiotics as adjuvant therapy for UC patients can regulate the balance of intestinal flora and reduce inflammatory responses.In UC patients with immune dysregulation,TLR4 and its signaling pathway is an important link to the pathogenesis of UC.The breakthrough of intestinal epithelial barrier by intestinal flora,the activation of immune system by various microbial antigens and the activation of inflammatory cells will lead to the inflammatory reactions in intestinal mucosal tissue of susceptible population.The process can be mediated by the TLR4-NF-κB signaling pathway.This paper reviews the treatment of UC with probiotics based on the TLR4-NF-κB signaling pathway.
Ulcerative colitis(UC)is a kind of nonspecific inflammatory diseases in the intestine,which is refractory and seriously affects the quality of life of patients.It is believed that the changes of intestinal flora are the main factors inducing and maintaining colonic inflammation.The clinical application of probiotics as adjuvant therapy for UC patients can regulate the balance of intestinal flora and reduce inflammatory responses.In UC patients with immune dysregulation,TLR4 and its signaling pathway is an important link to the pathogenesis of UC.The breakthrough of intestinal epithelial barrier by intestinal flora,the activation of immune system by various microbial antigens and the activation of inflammatory cells will lead to the inflammatory reactions in intestinal mucosal tissue of susceptible population.The process can be mediated by the TLR4-NF-κB signaling pathway.This paper reviews the treatment of UC with probiotics based on the TLR4-NF-κB signaling pathway.
引文
[1]欧阳钦,胡品津,钱家呜,等.对我国炎症性肠病诊断治疗规范的共识意见[J].现代消化及介入诊疗,2008,13(2):139-143.
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[5]张青波.益生菌联合美沙拉秦治疗溃疡性结肠炎的疗效和安全性观察[J].山西医药杂志,2018,47(1):76-77.
[6] Nell S,Suerbaum S,Josenhans C.The impact of the microbiota on the pathogenesis of IBD:Lessons from mouse infection models[J].Nat Rev Microbiol,2010,8(8):564-577.
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[10] LIU Xiubo,ZHANG Weiwei,XIE Xiangjun,et al.Expression of IL-6,IL-23and TGF-βin the mucosa of the ileum and ascending colon of patients with irritable bowel syndrome:An analysis of 110cases[J].World Chin J Digestol,2011,19(10):1085-1088.(in Chinese)刘修波,张巍巍,解祥军,等.肠黏膜细胞因子在肠易激综合征患者回肠及升结肠组织中的表达[J].世界华人消化杂志,2011,19(10):1085-1088.
[11] Masbukova A,Flavia A,Pedro J.Tumor necrosis factor alpha and inflammation disrupt the polarity complex in intestinal epithelial cells by aposttranslational mechanism[J].Mol Cell Biol,2011,31(4):756-765.
[12]钟燕敏,刘海燕,陈军贤,等.溃疡性结肠炎患者检测IL-1β、IL-6、IL-8的临床价值[J].浙江临床医学,2011,13(8):870-872.
[13] Reddy KP,Markowitz JE,Ruehelli ED,et al.Lamina propria and circulating interleukin-8in newly and previously diagnosed pediatric inflammatory bowel disease patients[J].Dig Dis Sci,2007,52(2):365-372.
[14] Yu ZH,Huang F,Xu N,et al.Expression of Toll-like receptor 4,CD14,and NF-κB in Chinese patients with ulcerative colitis[J].J Immunoassay Immunochem,2011,32(1):47-56.
[15] CHEN Xiao,WANG Qizhi.Progress of toll-like receptor 4signal transduction in ulcerative colitis[J].Chin J Gastroenterol Hepatol,2010,19(1):87-89.(in Chinese)陈晓,王启之.Toll样受体4的信号转导与溃疡性结肠炎的研究进展[J].胃肠病学和肝病学杂志,2010,19(1):87-89.
[16] Gribar SC,Anand RJ,Sodhi CP,et al.The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation[J].J Leukoc Biol,2008,83(3):493-498.
[17] Sang LX,Chang B,Zhang WL,et al.Remission induction and maintenance effect of probiotics on ulcerative colitis:A meta-analysis[J].World J Gastroeaterol,2010,16(15):1908-1915.
[18] SANG Lixuan,GAO Nan,ZHANG Dai,et al.Effects of VSL#3on TLR4and NF-κBp65expression of experimental colitis in rats[J].Chin J Gastroenterol Hepatol,2014,23(8):964-966.(in Chinese)桑力轩,高楠,张岱,等.益生菌VSL#3对大鼠实验性结肠炎大肠组织TLR4及NF-κBp65表达的影响[J].胃肠病学和肝病学杂志,2014,23(8):964-966
[19] LIAN Guanghui,CHEN Minhu,PENG Xiabiao,et al.Effects of L.acidophilus BCW and DNA on expression of NF-κB in murine with acute ulcerative colitis[J].Prog Mod Biomed,2011,11(3):468-471.(in Chinese)练光辉,陈旻湖,彭侠彪,等.嗜酸乳杆菌胞壁粗提物及DNA对实验性结肠炎结肠上皮NF-κB表达的影响[J].现代生物医学进展,2011,11(3):468-471.
[20] Lim SM,Kim DH.Bifidobacterium adolescentis IM38ameliorates high-fat diet-induced colitis in mice by inhibiting NF-κB activation and lipopolysaccharide production by gut microbiota[J].Nutr Res,2017,41:86-96.
[21] ZHAO Qihui,LI Gang,LI Mei,et al.Effect of probiotics intervention on gastrointestinal hormones,inflammatory mediators and expression of Toll like receptor 4in premature infants with necrotizing enterocolitis[J].Labeled Immunoassays Clin Med,2017,24(10):1154-1158.(in Chinese).赵启晖,李刚,李梅,等.益生菌干预对患坏死性小肠结肠炎早产儿胃肠激素、炎症介质及Toll样受体4表达水平的影响分析[J].标记免疫分析与临床,2017,24(10):1154-1158.
[22] Kaeid Sharaf L,Shukla G.Probiotics(Lactobacillus acidophilus and Lactobacillus rhamnosus GG)in conjunction with celecoxib(selective COX-2inhibitor)modulated DMH-induced early experimental colon carcinogenesis[J].Nutr Cancer,2018.DOI:10.1080/01635581.2018.1490783.
[2] Berg D,Clemente JC,Colombel JF.Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome?[J].Expert Rev Gastroenterol Hepatol,2015,9(6):781-795.
[3] Chen FE,Huang DB,Chen YQ,et al.Crystal structure of p50/p65heterodimer of transcription factor NF-κB bound to DNA[J].Nature,1998,391(6665):410-413.
[4] Kruis W,Schütz E,Fric P,et al.Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis[J].Aliment Pharmacol Ther,1997,11(5):853-858.
[5]张青波.益生菌联合美沙拉秦治疗溃疡性结肠炎的疗效和安全性观察[J].山西医药杂志,2018,47(1):76-77.
[6] Nell S,Suerbaum S,Josenhans C.The impact of the microbiota on the pathogenesis of IBD:Lessons from mouse infection models[J].Nat Rev Microbiol,2010,8(8):564-577.
[7] Avbelj M,Horvat S,Jerala R.The role of intermediary domain of MyD88in cell activation and therapeutic inhibition of TLRs[J].Immunology,2011,187(5):2394-2404.
[8] Chapman TM,Plosker GL,Figgitt DP.VSL#3probiotic mixture:A review of its use in chronic inflammatory bowel diseases[J].Drugs,2006,66(10):1371-1387.
[9] HE Bin,QIU Hongqing,CHENG Zhijian,et al.Expression level and clinical significance of Toll-like receptor 4and NFkappa B in peripheral blood monocytes of patients with ulcerative colitis[J].Chin J Clin Gastroenterol,2013,25(2):76-78.(in Chinese)何斌,邱洪清,程志健,等.溃疡性结肠炎患者外周血单核细胞中Toll样受体4、NF-κB的表达及其临床意义[J].临床消化病杂志,2013,25(2):76-78.
[10] LIU Xiubo,ZHANG Weiwei,XIE Xiangjun,et al.Expression of IL-6,IL-23and TGF-βin the mucosa of the ileum and ascending colon of patients with irritable bowel syndrome:An analysis of 110cases[J].World Chin J Digestol,2011,19(10):1085-1088.(in Chinese)刘修波,张巍巍,解祥军,等.肠黏膜细胞因子在肠易激综合征患者回肠及升结肠组织中的表达[J].世界华人消化杂志,2011,19(10):1085-1088.
[11] Masbukova A,Flavia A,Pedro J.Tumor necrosis factor alpha and inflammation disrupt the polarity complex in intestinal epithelial cells by aposttranslational mechanism[J].Mol Cell Biol,2011,31(4):756-765.
[12]钟燕敏,刘海燕,陈军贤,等.溃疡性结肠炎患者检测IL-1β、IL-6、IL-8的临床价值[J].浙江临床医学,2011,13(8):870-872.
[13] Reddy KP,Markowitz JE,Ruehelli ED,et al.Lamina propria and circulating interleukin-8in newly and previously diagnosed pediatric inflammatory bowel disease patients[J].Dig Dis Sci,2007,52(2):365-372.
[14] Yu ZH,Huang F,Xu N,et al.Expression of Toll-like receptor 4,CD14,and NF-κB in Chinese patients with ulcerative colitis[J].J Immunoassay Immunochem,2011,32(1):47-56.
[15] CHEN Xiao,WANG Qizhi.Progress of toll-like receptor 4signal transduction in ulcerative colitis[J].Chin J Gastroenterol Hepatol,2010,19(1):87-89.(in Chinese)陈晓,王启之.Toll样受体4的信号转导与溃疡性结肠炎的研究进展[J].胃肠病学和肝病学杂志,2010,19(1):87-89.
[16] Gribar SC,Anand RJ,Sodhi CP,et al.The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation[J].J Leukoc Biol,2008,83(3):493-498.
[17] Sang LX,Chang B,Zhang WL,et al.Remission induction and maintenance effect of probiotics on ulcerative colitis:A meta-analysis[J].World J Gastroeaterol,2010,16(15):1908-1915.
[18] SANG Lixuan,GAO Nan,ZHANG Dai,et al.Effects of VSL#3on TLR4and NF-κBp65expression of experimental colitis in rats[J].Chin J Gastroenterol Hepatol,2014,23(8):964-966.(in Chinese)桑力轩,高楠,张岱,等.益生菌VSL#3对大鼠实验性结肠炎大肠组织TLR4及NF-κBp65表达的影响[J].胃肠病学和肝病学杂志,2014,23(8):964-966
[19] LIAN Guanghui,CHEN Minhu,PENG Xiabiao,et al.Effects of L.acidophilus BCW and DNA on expression of NF-κB in murine with acute ulcerative colitis[J].Prog Mod Biomed,2011,11(3):468-471.(in Chinese)练光辉,陈旻湖,彭侠彪,等.嗜酸乳杆菌胞壁粗提物及DNA对实验性结肠炎结肠上皮NF-κB表达的影响[J].现代生物医学进展,2011,11(3):468-471.
[20] Lim SM,Kim DH.Bifidobacterium adolescentis IM38ameliorates high-fat diet-induced colitis in mice by inhibiting NF-κB activation and lipopolysaccharide production by gut microbiota[J].Nutr Res,2017,41:86-96.
[21] ZHAO Qihui,LI Gang,LI Mei,et al.Effect of probiotics intervention on gastrointestinal hormones,inflammatory mediators and expression of Toll like receptor 4in premature infants with necrotizing enterocolitis[J].Labeled Immunoassays Clin Med,2017,24(10):1154-1158.(in Chinese).赵启晖,李刚,李梅,等.益生菌干预对患坏死性小肠结肠炎早产儿胃肠激素、炎症介质及Toll样受体4表达水平的影响分析[J].标记免疫分析与临床,2017,24(10):1154-1158.
[22] Kaeid Sharaf L,Shukla G.Probiotics(Lactobacillus acidophilus and Lactobacillus rhamnosus GG)in conjunction with celecoxib(selective COX-2inhibitor)modulated DMH-induced early experimental colon carcinogenesis[J].Nutr Cancer,2018.DOI:10.1080/01635581.2018.1490783.