МЕХАНИЗМЫ ПОВРЕЖДАЮЩЕГО ДЕЙСТВИЯ ДЕКСТРАНСУЛЬФАТА НАТРИЯ В МОДЕЛИ ОСТРОГО ЯЗВЕННОГО КОЛИТА У МЫШЕЙ

DOI: https://doi.org/10.29296/24999490-2018-04-02

Т.И. Хомякова(1), кандидат медицинских наук, Н.А. Золотова(1), кандидат биологических наук, О.В. Макарова(1), доктор медицинских наук, профессор, Ю.Н. Хомяков(2), доктор биологических наук 1-ФГБНУ «Научно-исследовательский институт морфологии человека», Российская Федерация, 17418, Москва, ул. Цюрупы, д. 3; 2-ФКУЗ «Противочумный центр Роспотребнадзора», Российская Федеpация, 127490, Москва, ул. Мусоргского, д. 4 E-mail: tatkhom@yandex.ru

Использование декстрансульфата натрия (ДСН) в экспериментальной биологии и медицине в качестве индуктора экспериментального язвенного колита считается валидизированной моделью для оценки эффективности фармакологических препаратов, разрабатываемых с целью лечения воспалительных заболеваний кишечника человека. В данном обзоре обобщены результаты исследований механизмов патогенеза острого колита у мышей, представленных в научных публикациях последних лет. Понимание этих механизмов позволит разрабатывать препараты направленного действия для профилактики и лечения острых воспалительных заболеваний у человека и проводить их доклиническую оценку на адекватной модели.
Ключевые слова: 
декстрансульфат натрия, острый колит, воспаление, эпителиальный барьер, микробиом

Список литературы: 
  1. Осиков М.В., Симонян Е.В., Бакеева А.Е., Костина А.А. Экспериментальное моделирование болезни Крона и язвенного колита. Современные проблемы науки и образования. 2016; 4 URL: https:www.science-education.ru/ru/article/view?id=25072 (дата обращения: 31.01.2018). [Osykov M.V., Symonyan E.V., Bakeeva A.E., Kostyna T.I. Experimental modeling of Crone disease and ulcerative colitis. Modern problems of science and education. 2016; 4 (in Russian)]
  2. Абдулаева С.О., Кирюхин С.О., Белоусова Т.А., Хомякова Т.И., Черников В.П., Макарова О.В. Морфологическая характеристика острого язвенного колита, индуцированного декстрансульфатом натрия, у мышей линии Balb/с. Клиническая и экспериментальная морфология. 2012; 3: 32–40. [Abdullaeva S.O., Kiryukhin S.O., Belousova T.A., Kjomyakova T.I., Chernikov V.P., Makarova O.V. Morphological characteristic of severe dextran sodium sulphate induced ulcerative colitis in mice Balb/c. Kliinicheskaya I experimentalnaya morphologia. 2012; 3: 32–40 (in Russian)]
  3. Постовалова Е.А., Хочанский Д.Н., Золотова Н.А., Гао Ю., Макарова О.В., Добрынина М.Т. Морфологические изменения брыжеечных лимфатических узлов и субпопуляционный состав лимфоцитов при экспериментальном язвенном колите. Бюллетень экспериментальной биологии и медицины. 2015; 160 (12): 811–6. [Postovalova E.A., Khochansky D.N., Zolotova N.A., Gao Yu., Makarova O.V., Dobrynina M.T. Morphological changes of mesenteric lymphatic nodes at experimental ulcerative colitis. Bulletin of Experimental Biology and Medicine. 2015; 160 (12): 811–6 (in Russian)]
  4. Knod J.L., Crawford K., Dusing M., Frischer J.S. Murine colitis treated with multitargeted tyrosine kinase inhibitors. J. Surg. Res. 2016; 200 (2): 501–7.
  5. Золотова Н. А. Эпителиальный барьер ободочной кишки при экспериментальном язвенном колите. Журнал анатомии и гистопатологии. 2015; 4 (3): 54 [Zolotova N.A. Epithelial barrier of colon at experimental ulcerative colitis. J. of Anatomy and Histopathology. 2015; 4 (3): 54 (in Russian)]
  6. Torres-Aguilar L.,Rodriguez-Fragoso L.,Reyes-Esparza J.P. Pentosaceus administration attenuates the severity of dextran sulfate sodium-induced colitis and improve the intestinal permeability. Microbiol Res J. Int. 2017; 19 (4): 1–12.
  7. Helke K., Angel P., Lu P., Garrett-Mayer E, Ogretmen B, Drake R, Voelkel-Johnson C. Ceramide synthase 6 deficiency enhances inflammation in the DSS model of colitis. Sci Rep. 2018; 26; 8 (1): 1627. DOI: 10.1038/s41598-018-20102-z.
  8. Eichele D.D, Kharbanda K.K. Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World J. Gastroenterol. 2017; 23 (33): 6016–29.
  9. Chassaing B., Aitken J.D., Malleshappa M., Vijay-Kumar M..Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol. 2014; 4 (104): 15–25.
  10. Laroui H, Ingersoll S.A., Liu H. Ch., Baker M.T., Ayyadurai S., Charania M. A., Laroui F., Yan Yu., Sitaraman Sh. V., Merlin D. Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chainlength fatty acids in the colon. PLoS ONE | www.plosone.org 1 March 2012 | Volume 7 | Issue 3 | e32084.
  11. Yang H.-T., Chen J.-W., Rathod J.,.Jiang Yu-Z, Tsai P.-J., Hung Y.-P.,.Ko W.-Ch., Paredes-Sabja D., Huang I-H. Lauric acid is an inhibitor of Clostridium difficile growth in vitro and reduces inflammation in a mouse infection model. Front Microbiol. 2017; 8: 2635. Published online 2018 Jan 17. DOI: 10.3389/fmicb.2017.02635.
  12. Wong S.W., Kwon M.J., Choi A.M., Kim H.P., Nakahira K., Hwang D.H. Fatty acids modulate Toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner. J. Biol. Chem. 2009; 284: 27384–92.10.1074/jbc.M109.044065
  13. Lucas K., Maes M. Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol. Neurobiol. 2013; 48: 190–204. 10.1007/s12035-013-8425-7.
  14. Botham K.M., Wheeler-Jones C.P. Postprandial lipoproteins and the molecular regulation of vascular homeostasis. Prog Lipid Res. 2013; 52: 446–64. 10.1016/j.plipres.2013.06.001
  15. Basson A., Trotter A., Rodriguez-Palacios A., Cominelli F.Mucosal Interactions between Genetics, Diet, and Microbiome in Inflammatory Bowel Disease. Front Immunol. 2016; 7: 290. Published online 2016 Aug 2. DOI: 10.3389/fimmu.2016.00290
  16. Ariake K., Ohkusa T., Sakurazawa T., Kumagai J., Eishi Y., Hoshi S., Yajima T. Roles of mucosal bacteria and succinic acid in colitis caused by dextran sulfate sodium in mice. J. Med. Dent Sci. 2000; 47 (4): 233–41.
  17. Erickson N.A., Mundhenk L., Giovannini S., Glauben R., Heimesaat M.M., Gruber A.D. Role of goblet cell protein CLCA1 in murine DSS colitis. J. Inflamm (Lond). 2016; 4 (13): 5.
  18. Okumura R., Takeda K. Maintenance of gut homeostasis by the mucosal immune system. Proc Jpn. Acad Ser B Phys Biol. Sci. 2016; 92 (9): 423–35. Review.PMID:27840390 PMCID:PMC5328791 DOI:10.2183/pjab.92.423
  19. Johansson M.E., Phillipson M., Petersson J., Holm L., Velcich A., Hansson G.C. The inner of the two Muc2 mucin dependent mucus layers in colon is devoid of bacteria. Proc. Natl. Acad. Sci. USA. 2008; 105: 15064–9.
  20. Desai M.S., Seekatz A.M., Koropatkin N.M., Kamada N., Hickey C.A., Wolter M., Pudlo N.A., Kitamoto S., Terrapon N., Muller A., Young V.B., Henrissat B., Wilmes P., Stappenbeck T.S., Núñez G., Martens E.C. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016; 167 (5): 1339–53. e21. DOI: 10.1016/j.cell.2016.10.043.PMID:27863247
  21. Poritz L.S. Loss of the tight junction protein ZO-1 in dextran sulfate sodium induced colitis. L.S. Poritz, K.I. Garver, C. Green, L. Fitzpatrick, F. Ruggiero, W.A.,Koltun J. Surg. Res. 2007; 140: 12–9.
  22. Rodrigues-Sousa T., Ladeirinha A.F., Santiago A. R., Carvalheiro H., Raposo B., Alarcão A., Cabrita A., Holmdahl R., Carvalho L., Souto-Carneiro M.M. Deficient production of reactive oxygen species leads to severe chronic DSS-induced colitis in Ncf1/p47phox-mutant mice. PLoS One. 2014; 9 (5): e97532. Published online 2014 May 29. DOI: 10.1371/journal.pone.0097532.
  23. Gubernatorova E.О., Tumanov A.V. Tumor necrosis factor and lymphotoxin in regulation of intestinal inflammation Biochemistry (Moscow). 2016; 81 (11): 1309–25. ISSN 0006-2979, DOI: 10.1134/S0006297916110092.
  24. Sun X., Cai Y., Fleming C., Tong Z., Wang Z., Ding C., Qu M., Zhang H.G., Suo J., Yan J. Innate γδT17 cells play a protective role in DSS-induced colitis via recruitment of Gr-1+CD11b+ myeloid suppressor cells. Oncoimmunology. 2017; 6 (5): e1313369. DOI: 10.1080/2162402X.2017.1313369. eCollection 2017.
  25. Tun X., Yasukawa K., Yamada K. Involvement of nitric oxide with activation of Toll-like receptor 4 signaling inmice with dextran sodium sulfate-induced colitis. Free Radic Biol Med. 2014; 74: 108–17. DOI: 10.1016/j.freeradbiomed.2014.06.020. Epub 2014 Jun 30.
  26. Spehlmann M.E., Eckmann L. Nuclear factor-kappa B in intestinal protection and destruction. Curr. Opin. Gastroenterol. 2009; 25 (2): 92–9. DOI: 10.1097/MOG.0b013e328324f857.
  27. Kim J.-K., Lee S.H., Lee S.-Y., Kim E.-K., Kwon J.-E., Seo H.-B., et al. (2016) GRIM19 attenuates DSS induced colitis in an animal model. PLoS ONE 11(6): e0155853. https:doi.org/10.1371/journal.pone.0155853.
  28. Xiao Y.T., Yan W.H., Cao Y., Yan J.K., Cai W. Neutralization of IL-6 and TNF-α ameliorates intestinal permeability in DSS-induced colitis. Cytokine. 2016; 83: 189–92. DOI: 10.1016/j.cyto.2016.04.012. Epub 2016 May.
  29. Tian T., Zhou Y., Feng X., Ye S., Wang H., Wu W., Tan W., Yu C., Hu J., Zheng R., Chen Z., Pei X., Luo MicroRNA-16 is putatively involved in the NF-κB pathway regulation in ulcerative colitis through adenosine A2a receptor (A2aAR) mRNA targeting. Inf Sci Rep. 2016; 6: 30824. DOI: 10.1038/srep30824.
  30. Yao J., Wang J.Y., Liu L., Li Y.X., Xun A.Y., Zeng W.S., Jia C.H., Wei X.X., Feng J.L., Zhao L., Wang L.S. Anti-oxidant effects of resveratrol on mice with DSS-induced ulcerative colitis. Arch Med Res. 2010; 41 (4): 288–94. DOI: 10.1016/j.arcmed.2010.05.002.
  31. Peloquin J.M., Nguyen D.D. The microbiota and inflammatory bowel disease: Insights from animal models. Anaerobe. 2013; 24: 102–6.
  32. Hernández-Chirlaque C., Aranda C.J., Ocón B., Capitán-Cañadas F., Ortega-González M., Carrero J.J., Suárez M.D., Zarzuelo A., Sánchez de Medina F., Martinez-Augustin O. Germ-free and antibiotic-treated mice are highly susceptible to epithelial injury in DSS colitis. J. Crohns Colitis. 2016; 10 (11): 1324–35. Epub 2016 Apr 26.
  33. Li M., Wu Y., Hu Y., Zhao L., Zhang C. Initial gut microbiota structure affects sensitivity to DSS-induced colitis in a mouse model. Sci China Life Sci. 2017. DOI: 10.1007/s11427-017-9097-0.
  34. Rakoff-Nahoum S., Paglino J., Eslami-Varzaneh F., Edberg S., Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004; 118: 229–41.
  35. Rose W.A. 2nd, Sakamoto K., Leifer C.A. TLR9 is important for protection against intestinal damage and for intestinal repair. Sci Rep. 2012; 2: 574.
  36. Jin S., Zhao D., Cai C., Song D., Shen J., Xu A., Qiao Y., Ran Z., Zheng Q. Low-dose penicillin exposure in early life decreases Th17 and the susceptibility to DSS colitis in mice through gut microbiota modification. Sci Rep. 2017; 7: 43662. DOI: 10.1038/srep43662.
  37. Khajah M.A. The potential role of fecal microbiota transplantation in the treatment of inflammatory bowel disease. Scand J. Gastroenterol. 2017; 52 (11): 1172–84. DOI: 10.1080/00365521.2017.1347812. Epub 2017 Jul 7.
  38. Frank D.N., St Amand A.L., Feldman R.A., Boedeker E.C., Harpaz N., Pace N.R. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA. 2007; 104: 13780–5 [PMID: 17699621 DOI: 10.1073/pnas.070662510.
  39. Yang Y., Chen G., Yang Q., Ye J., Cai X., Tsering P.. Cheng X, Hu Ch., Zhang Sh., Cao P. Gut microbiota drives the attenuation of dextran sulphate sodium-induced colitis by Huangqin decoction inflammatory responses World J. Gastroenterol. 2012; 18 (19): 2344–56.
  40. Xiao-Li Huang Faecalibacterium prausnitzii supernatant ameliorates dextran sulfate sodium induced colitis by egulating Th17 cell differentiation. World Journal of Gastroenterol. 2016; 2 (22): 5201. DOI: 10.3748/wjg.v22.i22.5201.
  41. Gardlik R., Palffy R., Celec P. Recombinant probiotic therapy in experimental colitis in mice. Folia Biol. (Praha). 2012; 58 (6): 238–45.
  42. Dubey V., Ghosh A.R., Bishayee K., KhudaBukhsh A.R. Probiotic Pediococcus pentosaceus strain GS4 alleviates azoxymethane-induced toxicity in mice. Nutr Res. 2015; 35 (10): 921–9. DOI: 10.1016/j.nutres.2015.08.001.
  43. Zhang Z., Wu X., Cao S., Cromie M., Shen Y., Feng Y., Yang H., Li L. Chlorogenic acid ameliorates experimental colitis by promoting growth of Akkermansia in mice. Nutrients. 2017; 9 (7). DOI: 10.3390/nu9070677.
  44. Zhang Z., Wu X., Cao S., Wang L., Wang D., Yang H., Feng Y., Wang S., Li L. Caffeic acid ameliorates colitis in association with increased Akkermansia population in the gut microbiota of mice. Oncotarget. 2016; 7 (22): 31790–9. DOI: 10.18632/oncotarget.9306.
  45. Varyani F., Fleming J.O., Maizels R.M. Helminths in the gastrointestinal tract as modulators of immunity and pathology. Am. J. Physiol. Gastrointest Liver Physiol. 2017; 1; 312 (6): 537–49. DOI: 10.1152ajpgi.00024.2017. Epub 2017 Mar 16.
  46. Togre N., Bhoj P., Amdare N., Goswami K., Tarnekar A., Shende M. Immunomodulatory potential of recombinant filarial protein, rWbL2, and its therapeutic implication in experimental ulcerative colitis in mouse. Immunopharmacol Immunotoxicol. 2018; 7: 1–8. DOI: 10.1080/08923973.2018.1431925.
  47. Ajjampur S.S. R., Png Ch. W, Chia W. N., Zhang Yo., Tan K.S. W. Ex vivo and in vivo mice models to study Blastocystis spp. adhesion, colonization and pathology: closer to proving Koch’s postulates PLoS One. 2016; 11 (8): e0160458. Published online 2016 Aug 10. DOI: 10.1371/journal.pone.0160458
  48. Hatoum O.A., Binion D.G., Otterson M.F., Gutterman D.D. Acquired microvascular dysfunction in inflammatory bowel disease: loss of nitric oxide-mediated vasodilation. Gastroenterology. 125 (1): 58–69.
  49. Alkim C., Alkim H., Koksal A.R., Boga S., Sen I. Angiogenesis in Inflammatory Bowel Disease. Int. J. Inflam. 2015; 2015: 970890. DOI: 10.1155/2015/970890.