山东大学学报 (医学版) ›› 2018, Vol. 56 ›› Issue (9): 23-28.doi: 10.6040/j.issn.1671-7554.0.2018.186
• 临床医学 • 上一篇
李竹青,张文雪,李理想,王鹏,于岩波,左秀丽,李延青
LI Zhuqing, ZHANG Wenxue, LI Lixiang, WANG Peng, YU Yanbo, ZUO Xiuli, LI Yanqing
摘要: 目的 探究丁酸钠改善肠易激综合征(IBS)内脏高敏感性机制。 方法 纳入27例腹泻型肠易激综合征(IBS-D)患者及22例对照共49例参与者,免疫组化检测肠上皮IRAK1蛋白表达量,Spearman秩和检验分析IRAK1蛋白表达与腹痛程度和频率评分相关性。2,4,6-三硝基苯磺酸灌肠建立IBS疾病动物模型,丁酸钠灌肠干预,结肠扩张实验观察内脏敏感性变化,ELISA检测结肠IRAK1蛋白表达水平,Spearman秩和检验分析动物结肠IRAK1表达与内脏疼痛阈值相关性。以IL-33、丁酸钠干预HT-29细胞,Western blotting观察IRAK1蛋白表达变化。 结果 IBS-D患者结肠上皮IRAK1蛋白表达高于对照组,结肠上皮IRAK1表达水平与腹痛程度评分呈正相关(r=0.676, P<0.001),与腹痛频率评分呈正相关(r=0.725, P<0.001)。丁酸钠干预可降低IBS动物结肠IRAK1蛋白表达、提高内脏疼痛阈值,动物结肠IRAK1蛋白表达与内脏疼痛阈值呈负相关(r=-0.655,P<0.001)。IL-33可使细胞IRAK1蛋白表达上调,丁酸钠预处理可减弱此效应。 结论 丁酸钠可能通过下调IRAK1蛋白表达水平改善IBS内脏高敏感性。
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[1] Lehmann D, Radomski N, Lutke-Eversloh T. New insights into the butyric acid metabolism of Clostridium acetobutylicum[J]. Appl Microbiol Biotechnol, 2012, 96(5):1325-1339. [2] Vital M, Howe AC, Tiedje JM. Revealing the bacterial butyrate synthesis pathways by analyzing(meta)genomic data[J]. MBio, 2014, 5(2):e889. doi:10.1128/mBio.00889-14. [3] Kumari R, Ahuja V, Paul J. Fluctuations in butyrate-producing bacteria in ulcerative colitis patients of North India[J]. World J Gastroenterol, 2013, 19(22):3404-3414. [4] Van den Abbeele P, Belzer C, Goossens M, et al. Butyrate-producing clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model[J]. ISME, 2013, 7(5):949-961. [5] Mishiro T, Kusunoki R, Otani A, et al. Butyric acid attenuates intestinal inflammation in murine DSS-induced colitis model via milk fat globule-EGF factor 8[J]. Lab Invest, 2013, 93(7):834-843. [6] Pozuelo M, Panda S, Santiago A, et al. Reduction of butyrate- and methane-producing microorganisms in patients with irritable bowel syndrome[J]. Sci Rep, 2015, 5:12693. doi:10.1038/srep12693. [7] Jain A, Kaczanowska S, Davila E. IL-1 receptor-associated kinase signaling and its role in inflammation, cancer progression, and therapy resistance[J]. Front Immunol, 2014, 5:553. doi:10.3389/fimmu.2014.00553. [8] Heiseke AF, Jeuk BH, Markota A, et al. IRAK1 drives intestinal inflammation by promoting the generation of effector the cells with optimal gut-homing capacity[J].J Immunol, 2015, 195(12):5787-5794. [9] Jin Z, Liang F, Yang J, et al. hnRNP I regulates neonatal immune adaptation and prevents colitis and colorectal cancer[J]. PLoS Genet, 2017,13(3):e1006672. doi:10.1371/journal.pgen.1006672. [10] Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders[J]. Gastroenterology, 2006, 130(5):1480-1491. [11] Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome[J]. Gastroenterology, 2004, 126(3):693-702. [12] Liu Y, Xu Y, Ma H, et al. Hepatitis B virus X protein amplifies TGF-beta promotion on HCC motility through down-regulating PPM1a[J]. Oncotarget, 2016, 7(22):33125-33135. [13] Qi QQ, Chen FX, Zhao DY, et al. Colonic mucosal N-methyl-D-aspartate receptor mediated visceral hypersensitivity in a mouse model of irritable bowel syndrome[J]. J Dig Dis, 2016, 17(7):448-457. [14] Zhou Q, Yang L, Larson S, et al. Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1[J]. GUT, 2016, 65(5):797-805. [15] Defrees DN, Bailey J. Irritable bowel syndrome: epidemiology, pathophysiology, diagnosis, and treatment[J]. Prim Care, 2017, 44(4):655-671. [16] Hungin AP, Paxman L, Koenig K, et al. Prevalence, symptom patterns and management of episodic diarrhea in the community:a population-based survey in 11 countries[J]. Aliment Pharmacol Ther, 2016, 43(5):586-595. [17] Simren M, Barbara G, Flint HJ, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report[J]. GUT, 2013, 62(1): 159-176. [18] Moraru IG, Moraru AG, Dumitrascu DL. Irritable bowel syndrome and the small intestinal microflora. What do we know?[J]. Rom J Intern Med, 2015, 53(1):103-107. [19] Camilleri M, Madsen K, Spiller R, et al. Intestinal barrier function in health and gastrointestinal disease[J]. Neurogastroenterol Motil, 2012, 24(6):503-512. [20] Sinagra E, Pompei G, Tomasello G, et al. Inflammation in irritable bowel syndrome: Myth or new treatment target?[J]. World J Gastroenterol, 2016, 22(7):2242-2255. [21] Brown K, Abbott DW, Uwiera RRE, et al. Removal of the cecum affects intestinal fermentation, enteric bacterial community structure, and acute colitis in mice[J]. Gut Microbes, 2018, 9(3):218-235. [22] Zheng L, Kelly CJ, Battista KD, et al. Microbial-derived butyrate promotes epithelial barrier function through IL-10 receptor-dependent repression of claudin-2[J]. J Immunol, 2017, 199(8):2976-2984. [23] Zaleski A, Banaszkiewicz A, Walkowiak J. Butyric acid in irritable bowel syndrome[J]. Prz Gastroenterol, 2013, 8(6):350-353. [24] Elce A, Amato F, Zarrilli F, et al. Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells[J]. Benef Microbes, 2017, 8(5):841-847. [25] Vollmer S, Strickson S, Zhang T, et al. The mechanism of activation of IRAK1 and IRAK4 by interleukin-1 and Toll-like receptor agonists[J]. Biochem J, 2017, 474(12):2027-2038. [26] Zhao Q, Chen G. Role of IL-33 and its receptor in T cell-mediated autoimmune diseases[J]. Biomed Res Int, 2014, 2014:587376. doi:10.1155/2014/587376. |
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