[Frontiers In Bioscience, Landmark, 23, 2166-2176, June1, 2018]

Establishment of a porcine model of indomethacin-induced intestinal injury

Dan Yi1, Wenkai Liu1, Yongqing Hou1, Lei Wang1, Di Zhao1, Tao Wu1, Binying Ding1, Guoyao Wu1,2

1Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China; 2Department of Animal Science, Texas A&M University, College Station, TX, USA 77843


1. Abstract
2. Introduction
3. IDMT induced intestinal injury of piglets
3.1. General study protocol
3.2. Changes in the body weight of piglets challenged with IDMT
3.3. Changes in the hematological indexes of piglets challenged with IDMT
3.4. Intestinal lesions and alterations of intestinal histology in piglets challenged with IDMT
3.5. Redox status in the plasma and intestine challenged with IDMT
3.6. Variation of gene expression profiles in the intestinal mucosa challenged with IDMT
4. Conclusion and perspectives
5. Acknowledgements
6. References


A useful animal model of intestinal injury is pivotal for studying its pathogenesis and developing nutritional interventions (e.g., amino acid supplementation). Here, we propose the use of indomethacin (IDMT) to induce intestinal inflammation in neonatal pigs. Fourteen-day-old piglets fed a milk replacer diet receive intraperitoneal administration of IDMT (5 mg/kg body weight) for 3 consecutive days. On day 4, blood and intestinal samples are obtained for physiological and biochemical analyses. IDMT increases blood DAO activity, I-FABP concentration, neutrophil and eosinophil numbers; intestinal MMP3 mRNA levels, MPO activity, and MDA concentration; but reduces the plasma concentration of citrulline (synthesized exclusively by enterocytes of the small intestine), intestinal GSH-Px activity, and mRNA levels for villin, I-FABP, TRPV6, AQP10, and KCNJ13. Moreover, extensive hemorrhagic spots, thinned intestinal wall, and ulcers in the distal jejunum and ileum are observed in IDMT-challenged piglets. Furthermore, IDMT decreases intestinal villus height and villus surface area in the piglet jejunum. Collectively, this work establishes a porcine model of intestinal injury for designing novel nutritional means to improve gut function in pigs and humans.


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Abbreviations: ADG, average daily gain; ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; AQP10, aquaporin 10; BASO, basophils; CHOL, cholesterol; DAO, diamine oxidase; EOS, eosinophils; GSH-Px, glutathione peroxidase; H2O2, hydrogen peroxide; I-FABP, intestinal fatty acid-bonding protein; IL-8, interleukin 8; KCNJ13, potassium inwardly-rectifying channel, subfamily J, member 13; LYM, lymphocytes; MDA, malonaldehyde; MMP3, matrix metalloproteinase-3; MONO, monocytes; MPO, myeloperoxidase; NEUT, neutrophils; pBD-1, porcine β-defense 1; PLT, platelets; RBC, red blood cells; SOD, superoxide dismutase; TBIL, total bilirubin; TG, triglycerides; TP, total protein; TRPV6, transient receptor potential cation channel, subfamily V, member 6; WBC, white blood cells.

Key Words: Hematology, Indomethacin, Inflammation, Intestinal injury, Animal Model, Piglets, Review

Send correspondence to: Yongqing Hou, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China, Tel: 86 2783956175, Fax: 86 2783956175, E-mail: houyq@aliyun.com