Dietary Epidermal Growth Factor Supplementation Alleviates Intestinal Injury in Piglets with Intrauterine Growth Retardation via Reducing Oxidative Stress and Enhancing Intestinal Glucose Transport and Barrier Function

Abstract

EGF plays an important role in the intestinal repair and nutrients transport of animals. However, the effect of EGF on the intestinal health of piglets with IUGR has not been reported. Thus, the present study was performed to investigate the effects of EGF on the intestinal morphology, glucose absorption, antioxidant capacity, and barrier function of piglets with IUGR. A total of 6 NBW piglets and 12 IUGR piglets were randomly divided into three treatments: NC group (NBW piglets fed with basal diet, n = 6), IC group (IUGR piglets fed with basal diet, n = 6), and IE group (IUGR piglets fed with basal diet supplemented with 2 mg/kg EGF, n = 6). Growth performance, serum biochemical profile, jejunum histomorphology, jejunum glucose absorption and antioxidant capacity, and jejunal barrier function were measured. The results showed that EGF supplementation significantly increased the final body weight (FBW), average daily gain (ADG), and average daily feed intake (ADFI) of piglets with IUGR; EGF supplementation significantly increased the total protein (TP), glucose (GLU), and immunoglobulin G (IgG) levels compared with the IUGR piglets in the IC group; EGF administration effectively exhibited an increased jejunum villus height (VH) and the villus-height-to-crypt-depth ratio (V/C) of IUGR piglets compared with the IC group; EGF supplementation significantly increased sodium/potassium-transporting adenosine triphosphatase (Na⁺/K⁺-ATPase) activity, intestinal alkaline phosphatase (AKP) activity, glucose transporter sodium/glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2), and AMP-activated protein kinase α1 (AMPK-α1) mRNA expressions in the jejunum of IUGR piglets compared with the IC group; EGF supplementation exhibited increased superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC) levels, tended to increase glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and tended to decrease the malondialdehyde (MDA) level in the jejunum of IUGR piglets compared with the IC group; EGF supplementation significantly increased ZO-1, Claudin-1, Occludin, and MUC2 mRNA expressions and improved secreted immunoglobulin A (sIgA) secretion in the jejunum of IUGR piglets compared with the IC group and tended to decrease the interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) levels in the jejunum of IUGR piglets compared with the IC group. Pearson's correlation analysis further showed that EGF can promote intestinal development and nutrient absorption by promoting intestinal barrier function, thus improving the growth performance of IUGR piglets.

Keywords: epidermal growth factor; glucose absorption; intestinal barrier function; intrauterine growth retardation; oxidative stress; piglets.

Figure 1

Effects of EGF on the jejunum morphology of piglets with IUGR. (A) villus height, (B) crypt depth, (C) villus height to crypt depth, (D) correlations analysis between intestinal morphology and growth performance. Values are expressed as means ± SEM, n = 6 (one pig in the IC group was dead, n = 5 in IC group); NC: NBW piglets fed with basal diet; IC: IUGR piglets fed with basal diet; IE: IUGR piglets fed with basal diet supplemented with 2 mg/kg EGF. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 2

Effects of EGF on the intestinal glucose absorption capacity of piglets with IUGR. (A) Na⁺/K⁺-ATPase activity, (B) AKP activity, (C) SGLT1 mRNA, (D) GLU2 mRNA, (E) AMPK-α1 mRNA, (F) correlations analysis between intestinal glucose absorption capacity and growth performance, (G) correlations analysis between intestinal glucose absorption capacity and intestinal morphology. Values are expressed as means ± SEM, n = 6 (1 pig in the IC group was dead, n = 5 in the IC group); NC: NBW piglets fed with basal diet; IC: IUGR piglets fed with basal diet; IE: IUGR piglets fed with basal diet supplemented with 2 mg/kg EGF. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 3

Effects of EGF on the intestinal antioxidant capacity of piglets with IUGR. (A) SOD, (B) GSH-Px, (C) CAT, (D) T-AOC, (E) MDA, (F) correlation analysis between intestinal antioxidant capacity and growth performance, (G) correlation analysis between intestinal antioxidant capacity and intestinal morphology. Values are expressed as means ± SEM, n = 6 (1 pig in the IC group was dead, n = 5 in the IC group); NC: NBW piglets fed with basal diet; IC: IUGR piglets fed with basal diet; IE: IUGR piglets fed with basal diet supplemented with 2 mg/kg EGF. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 4

Effects of EGF on the intestinal barrier function of piglets with IUGR. (A) MUC2 mRNA, (B) ZO-1 mRNA, (C) Claudin-1 mRNA, (D) Occludin mRNA, (E) sIgA level, (F) IL-1β level, (G) IL-6 level, (H) TNF-α level, (I) correlation analysis between intestinal barrier function and growth performance, and (J) correlation analysis between barrier function and intestinal morphology. Values are expressed as means ± SEM, n = 6 (1 pig in the IC group was dead, n = 5 in the IC group); NC: NBW piglets fed with basal diet; IC: IUGR piglets fed with basal diet; IE: IUGR piglets fed with basal diet supplemented with 2 mg/kg EGF. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 5

Correlation analysis between intestinal barrier function and intestinal glucose absorption capacity. * p < 0.05, ** p < 0.01, *** p < 0.001.