Electroacupuncture alleviates water avoidance stress-induced irritable bowel syndrome in mice by improving intestinal barrier functions and suppressing the expression of inflammatory cytokines

  • Mengzhu SUN ,
  • Yujie ZHANG ,
  • Yafang SONG ,
  • Jing GUO ,
  • Yuhang WANG ,
  • Chen XIN ,
  • Dongmei GU ,
  • Jianhua SUN ,
  • Lixia PEI
Expand
  • 1 Department of acupuncture, Affiliated Hospital of Nanjing University of Chinese Meidicne, Nanjing 210023, China
    2 Department of acupuncture, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China

Received date: 2021-02-12

  Accepted date: 2021-05-07

  Online published: 2023-04-28

Supported by

Research and Practice Innovation Program for Postgraduates of Jiangsu Province (Mechanism of Electroacupuncture Regulating Bile Acid Receptor to Alleviate Visceral Hypersensitivity in Irritable Bowel Syndrome)(KYCX20_1469);National Natural Science Fund (Mechanism of Electroacupuncture Regulating CRF-NLRP6 Inflammasome-Related Pathways in Intestinal Flora Immune Dialogue)(81804193);Leading Talents Project of Jiangsu Provincial Administration of TCM (Clinical Effect and Mechanism of Acupuncture and Moxibustion on Irritable Bowel Syndrome)(SLJ0206);Peak Talent Project of Jiangsu Province Hospital of TCM (Clinical Effect and Mechanism of Acupuncture and Moxibustion in the Treatment of Functional Gastrointestinal Diseases)(y2018rc05)

Abstract

OBJECTIVE: To evaluate the effects and related mechanisms of electroacupuncture (EA) on irritable bowel syndrome (IBS).

METHODS: Male C57BL/6 mice were randomly allocated into normal, model, and EA groups. Experimental IBS mice models were established by exposure to water avoidance stress (WAS). Mice in the EA group were treated with EA at bilateral Tianshu (ST 25) and Zusanli (ST 36) for 7 consecutive days, 15 min each day. Abdominal withdrawal reflex (AWR) tests and intestinal motility tests were performed to evaluate visceral sensitivity and intestinal motility of mice. Expression levels of tight junction proteins (TJPs) and inflammatory cytokines in colon tissues were determined through immunofluorescence, real-time polymerase chain reactions (PCR) and Western blot assays.

RESULTS: EA alleviated visceral hypersensitivity and intestinal hypermotility in WAS-induced IBS mice. Moreover, EA promoted the expression of zonula occludens (ZO)-1, claudin-1, and occludin while suppressing the expression of interleukin (IL)-8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-αin water avoidance stress (WAS)-induced irritable bowel syndrome (IBS) mice.

CONCLUSION: EA alleviated WAS-induced IBS in mice by promoting intestinal barrier functions and suppressing the expression of inflammatory cytokines.

Cite this article

Mengzhu SUN , Yujie ZHANG , Yafang SONG , Jing GUO , Yuhang WANG , Chen XIN , Dongmei GU , Jianhua SUN , Lixia PEI . Electroacupuncture alleviates water avoidance stress-induced irritable bowel syndrome in mice by improving intestinal barrier functions and suppressing the expression of inflammatory cytokines[J]. Journal of Traditional Chinese Medicine, 2023 , 43(3) : 494 -500 . DOI: 10.19852/j.cnki.jtcm.2023.03.001

References

[1] Sultan S, Malhotra A. Irritable bowel syndrome. Ann Intern Med 2017; 166: C81-96.
[2] Posserud I, Syrous A, Lindstrom L, et al. Altered rectal perception in irritable bowel syndrome is associated with symptom severity. Gastroenterology 2007; 133: 1113-23.
[3] Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol 2017; 11: 821-34.
[4] Bertiaux-Vandaele N, Youmba SB, Belmonte L, et al. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol 2011; 106: 2165-73.
[5] Nozu T, Miyagishi S, Nozu R, et al. Losartan improves visceral sensation and gut barrier in a rat model of irritable bowel syndrome. Neurogastroenterol Motil 2020; 32: e13819.
[6] Nusrat A, Turner JR, Madara JL. Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am J Physiol Gastrointest Liver Physiol 2000; 279: G851-7.
[7] Patel SR, Singh A, Misra V, et al. Levels of interleukins 2, 6, 8, and 10 in patients with irritable bowel syndrome. Indian J Pathol Microbiol 2017; 60: 385-9.
[8] de Souza HS, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol 2016; 13: 13-27.
[9] Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014; 14: 329-42.
[10] Madara JL, Stafford J. Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest 1989; 83: 724-27.
[11] Mullin JM, Laughlin KV, Marano CW, et al. Modulation of tumor necrosis factor-induced increase in renal (LLC-PK1) transepithelial permeability. Am J Physiol 1992; 263: F915-24.
[12] Milard M, Penhoat A, Durand A, et al. Acute effects of milk polar lipids on intestinal tight junction expression: towards an impact of sphingomyelin through the regulation of IL-8 secretion? J Nutr Biochem 2019; 65: 128-38.
[13] Song YF, Geng H, Chen L, et al. Electroacupuncture relieves irritable bowel syndrome by increasing expression of nucleotide-binding oligomerization domain protein-like receptor family pyrin domain containing 6 in water-avoidance stress mice. J Tradit Chin Med 2020; 40: 407-13.
[14] Fourie NH, Wang D, Abey SK, et al. Structural and functional alterations in the colonic microbiome of the rat in a model of stress induced irritable bowel syndrome. Gut Microbes 2017; 8: 33-45.
[15] Ren X, Liu L, Gamallat Y, et al. Enteromorpha and polysaccharides from enteromorpha ameliorate loperamide-induced constipation in mice. Biomed Pharmacother 2017; 96: 1075-81.
[16] Rojas-Macias V, Rodriguez-Fandino O, Jimenez-Ponce F, et al. External validity of a relevant model for irritable bowel syndrome (IBS) using chronic stress by water avoidance in Wistar rats. Rev Gastroenterol Mex 2010; 75: 421-6.
[17] Song YF, Pei LX, Chen L, et al. Electroacupuncture relieves irritable bowel syndrome by regulating IL-18 and gut microbial dysbiosis in a trinitrobenzene sulfonic acid-induced post-inflammatory animal model. Am J Chin Med 2020; 48: 77-90.
[18] Chen Y, Zhao Y, Luo DN, et al. Electroacupuncture regulates disorders of gut-brain interaction by decreasing corticotropin-releasing factor in a rat model of IBS. Gastroenterol Res Pract 2019; 1759842.
[19] Zhang F, Ma Z, Weng Z, et al. P2X3 receptor in primary afferent neurons mediates the relief of visceral hypersensitivity by electroacupuncture in an irritable bowel syndrome rat model. Gastroenterol Res Pract 2020; 8186106.
[20] Du MH, Luo HM, Hu S, et al. Electroacupuncture improves gut barrier dysfunction in prolonged hemorrhagic shock rats through vagus anti-inflammatory mechanism. World J Gastroenterol 2013; 19: 5988-99.
[21] Pope JL, Bhat AA, Sharma A, et al. Claudin-1 regulates intestinal epithelial homeostasis through the modulation of Notch-signalling. Gut 2014; 63: 622-34.
[22] Coeffier M, Gloro R, Boukhettala N, et al. Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol 2010; 105: 1181-8.
[23] Piche T. Tight junctions and IBS-the link between epithelial permeability, low-grade inflammation, and symptom generation? Neurogastroenterol Motil 2014; 26: 296-302.
[24] Bertiaux-Vandaele N, Youmba SB, Belmonte L, et al. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol 2011; 106: 2165-73.
[25] Sinagra E, Morreale GC, Mohammadian G, et al. New therapeutic perspectives in irritable bowel syndrome: targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond. World J Gastroenterol 2017; 23: 6593-627.
[26] Choghakhori R, Abbasnezhad A, Hasanvand A, et al. Inflammatory cytokines and oxidative stress biomarkers in irritable bowel syndrome: association with digestive symptoms and quality of life. Cytokine 2017; 93: 34-43.
[27] Ji LJ, Li F, Zhao P, et al. Silencing interleukin 1alpha underlies a novel inhibitory role of miR-181c-5p in alleviating low-grade inflammation of rats with irritable bowel syndrome. J Cell Biochem 2019; 120: 15268-79.
[28] Yang J, Shang B, Shi H, et al. The role of toll-like receptor 4 and mast cell in the ameliorating effect of electroacupuncture on visceral hypersensitivity in rats. Neurogastroenterol Motil 2019; 31: e13583.
[29] Xu D, Gao J, Gillilland MR, et al. Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats. Gastroenterology 2014; 146: 484-96.
[30] de Magalhaes SF, Manzo LP, de Faria FM, et al. Inflammatory pain in peripheral tissue depends on the activation of the TNF-alpha type 1 receptor in the primary afferent neuron. Eur J Neurosci 2021; 53: 376-89.
[31] Zhen Y, Chu C, Zhou S, et al. Imbalance of tumor necrosis factor-alpha, interleukin-8 and interleukin-10 production evokes barrier dysfunction, severe abdominal symptoms and psychological disorders in patients with irritable bowel syndrome-associated diarrhea. Mol Med Rep 2015; 12: 5239-45.
[32] Barbaro MR, Di Sabatino A, Cremon C, et al. Interferon-gamma is increased in the gut of patients with irritable bowel syndrome and modulates serotonin metabolism. Am J Physiol Gastrointest Liver Physiol 2016; 310: G439-47.
Outlines

/