Effects Of Tributyrin On Acetic Acid-induced Colitis Of Piglets And Its Mechanism

The aim of this study was to establish acetic acid-induced colitis model inpiglets, and investigate the effects of dietary Tributyrin (TB) on growthperformance, intestinal trauma, immunological stress, intestinal barrier functionand antioxidant capactiy in piglets with acetic acid-induced colitics.1. Establishment of an acetic acid-induced colitis model in pigletsEighteen healthy piglets (Duroc×Landrace×Large white) were administeredsaline (control group,3piglets), trinitrobenzene sulfonic acid (TNBS group,6piglets) or acetic acid (acetic acid group,9piglets). Control group wereintrarectally administered10mL saline;3piglets in TNBS group wereintrarectally administered with25mg/kg BW TNBS, the others were intrarectallyadministered with50mg/kg BW TNBS;3piglets in acetic acid group wereintrarectally administered with10mL5%acetic acid, the others were intrarectallyadministered with10mL10%acetic acid. The general conditions of piglets andfeces were observed after administration. Three or seven days after intrarectaladministration, piglets were sacrificed to obtain colon for analysis. There wassignificant inflammatory response on feces situation, colon general situation andhistological measurements in the piglets with intrarectal administration of10%acetic acid. Three days after intrarectal administration, the colonic mucosa ofpiglets with intrarectal administration of10%acetic acid appeared ulcerations andobvious inflammatory cell infiltration; Seven days after intrarectal administration,the ulcerations were off, inflammatory cell infiltration significantly reduced, and alarge number of fibroblast cell hyperplasia occurred. The results indicated thatintrarectal administration of10%acetic acid can successfully induce colitis inpiglets.2. Effects of TB on growth performance, hematological parameters, andrelated blood parameters of piglets with acetic acid-induced colitics.Eighteen healthy piglets were randomly assigned to three treatment groups: (1) control group,(2) Acetic Acid group,(3) TB group.6replicates per treatmentgroup with one pig per replicate. The control and Acetic Acid group were fed thebasal diet, TB group was fed the basal diet supplemented with0.1%TB. On d15,piglets in the Acetic Acid and0.1%TB groups were intrarectally administeredwith10mL10%acetic acid, whereas piglets in the control group wereintrarectally administered with the same volume of physiological saline. Bloodsamples were collected on d18and d21. All the piglets were sacrificed on d22tocollect samples for analysis.The results showed that:(1) Dietary supplementation with TB increased theaverage daily gain (ADG)(P=0.089), reduced the ratio of feed to gain (F/G)(P<0.05) during d0to d14.(2) Acetic Acid challenge increased NEU (P<0.05) inblood samples3days after challenge. Acetic Acid challenge increased WBC, LYMand NEU (P<0.05), whereas dietary supplementation with TB reduced HGBcontent, LYMR and LYM (P<0.05) in blood samples6days after challenge.(3)Acetic Acid challenge increased BUN, CREA (P<0.05), whereas dietarysupplementation with TB reduced BUN (P<0.05) in blood samples3days afterchallenge. Acetic Acid challenge increased AST (P<0.05), whereas dietarysupplementation with TB reduced AST (P<0.05) in blood samples6days afterchallenge.(4) Acetic Acid challenge reduced INS (P<0.05), whereas dietarysupplementation with TB increased INS (P<0.05) in blood samples6days afterchallenge. In conclusion, dietary supplementation with TB can effectively improvegrowth performance of piglets, also alleviate negative effects of Acetic Acidchallenge on hematological parameters, blood biochemical parameters, and relatedplasma hormones.3. Effects of TB on immunological stress and antioxidant capactiy in pigletswith acetic acid-induced colitics.The results showed that:(1) Acetic Acid challenge increased PGE2, TNF-α(P<0.05) in blood samples6days after challenge. Acetic Acid challenge increasedPGE2, TNF-α (P<0.05), whereas dietary supplementation with TB reduced PGE2 (P<0.05) in colon mucosa.(2) Acetic Acid challenge reduced goblet cell ratio,increased IEL, LYMD (P<0.05), whereas dietary supplementation with TBincreased goblet cell ratio, reduced IEL, LYMD (P<0.05) in colon mucosa.(3)Acetic Acid challenge increased MPO，iNOS activity and MDA content (P<0.05),whereas dietary supplementation with TB reduced iNOS activity and MDA contentin blood samples3days after challenge (P<0.05). Acetic Acid challenge increasedMDA content (P<0.05), whereas dietary supplementation with TB reduced MDAcontent in blood samples6days after challenge (P<0.05). Acetic Acid challengereduced CAT activity (P<0.05), whereas dietary supplementation with TBincreased CAT activity in colon mucosa (P<0.05).(4) Acetic Acid challengeincreased NF-κB mRNA relative expression in jejunal mucosa, reduced TNF-α andTLR4mRNA relative expression in ileum mucosa (P<0.05), reduced TNF-αmRNA relative expression in colon mucosa, whereas dietary supplementation withTB increased TNF-α mRNA relative expression in ileum and colon mucosa(P<0.05). In conclusion, dietary supplementation with TB can effectively alleviatenegative effects of Acetic Acid challenge on immunological stress and antioxidantcapactiy.4. Effects of TB on immunological stress and antioxidant capactiy in pigletswith acetic acid-induced colitics.The results showed that:(1) Acetic Acid challenge increased crypt depth andreduced the ratio of villus height to crypt depth in duodenal mucosa, reduced thevillus height and the villous surface area in jejunal mucosa, reduced the ratio ofvillus height to crypt depth in ileum mucosa (P<0.05), whereas dietarysupplementation with TB reduced crypt depth, increased the ratio of villus heightto crypt depth and the villous surface area in duodenal mucosa (P<0.05).(2)Acetic Acid challenge increased DAO activity in in blood samples6days afterchallenge.(3) Acetic Acid challenge increased RNA/DNA and reduced TP/DNA(P<0.05), whereas dietary supplementation with TB reduced DNA content andincreased TP/DNA in jejunal mucosa (P<0.05).(4) Acetic Acid challenge increased the activity of maltase and sucrose (P<0.05), Whereas dietarysupplementation with TB reduced the activity of maltase and sucrase in ileummucosa (P<0.05).(5) Acetic Acid challenge increased caspase-3relativeexpression and reduced claudin-1relative expression (P<0.05), whereas dietarysupplementation with TB reduced caspase-3relative expression and increasedclaudin-1relative expression in colon mucosa (P<0.05).(6) Acetic Acid challengeincreased EGF mRNA relative expression in colon (P<0.05) and jejunal (P<0.1)mucosa, whereas dietary supplementation with TB reduced EGF mRNA relativeexpression in colon (P<0.05) and jejunal (P<0.1) mucosa. In conclusion, dietarysupplementation with TB can effectively alleviate negative effects of Acetic Acidchallenge on cell apoptosis, the injury of intestinal barrier function, promote cellproliferation and growth, which may be associated with the cell apoptosissignaling, EGF signaling and expression of tight junction protein.