| Experiment 1:Effects of high nutrient intake on intestinal development and immune function in piglets with intrauterine growth restrictionIntrauterine growth restriction (IUGR) leads to the impaired gastrointestinal tract of mammalian, and seriously delays the postnatal development. High nutritient intake (HNI) promoted the rapid growth of IUGR neonates, but aggravated postnatal metabolic syndrome. The objective of this study was to investigate the effects of HNI on intestinal morphology and immune function of IUGR and normal-birth weight (NBW) piglets.Twelve IUGR and 12 NBW piglets at 7 day of age were allocated randomly to basic nutrient-level group or a high nutrient-level group, whose nutrient contents were about 1.5-fold those of the former, according to a 2×2 experimental design, which gave 6 replicates per treatment with 1 piglet per replicate. The trial lasted for 21 days. The results showed that IUGR significantly decreased serum concentrations of TNF-α and IL-1β, as well as the ratios of TNF-α:IL-10 and IL-1β:IL-10 in piglets (P<0.01). IUGR decreased the intestinal villous height:crypt depth ratio (VCR) in piglets (P<0.05). The mRNA abundance of Toll-like receptor (TLR)-4, TLR-9, TNF receptor-associated factor 6 (TRAF-6), IL-1β and Toll-interacting protein (TOLLIP) was decreased in the ileum of IUGR piglets relative to NBW piglets (P<0.05). Regardless of BW, HNI significantly decreased the count of neutrophil (P<0.05), IL-1β concentration as well as the ratios of TNF-α:IL-10 and IL-1β:IL-10 (P<0.01). Moreover, HNI decreased the mRNA abundance of NF-κB and IL-1β (P<0.05), but increased TLR-9 mRNA expression in the ileum (P<0.01). Furthermore, compared with ANI, HNI significantly decreased the mRNA abundance of TLR-4 and NF-κB in the ileum of IUGR piglets, meanwhile, the mRNA abundance of TOLLIP was significantly decreased in the ileum of IUGR and NBW piglets by HNI, which implied that HNI impaired the expressions of innate immunity-related genes in the ileum, especially in piglets with IUGR. In summary, IUGR led to impaired intestinal development and innate immune function, however, HNI was not beneficial for the immune function of IUGR piglets during the early postnatal period.Experiment 2:Effects of restricted nutrient intake on the growth performance, intestinal development and immune function of piglets withintrauterine growth restrictionThe current study was to investigate the effects of postnatal nutritional restriction on the growth performance, intestinal development and immune function of neonates with IUGR using piglets as model. Twelve IUGR and 12 NBW piglets at 7 day of age were allocated randomly to control group (ANI) or feed restriction group (RNI) according to a 2×2 experimental design, which gave 6 replicates per treatment with 1 piglet per replicate. Among them, IUGR-ANI and NBW-ANI piglets were fed ad libitum. NBW-RNI piglets were provided the same amount of nutrient as IUGR-ANI piglets, while the amount of nutrient provided for IUGR-RNI piglets was according to the calculation that the average nutrient intake of IUGR-ANI piglets multiplied the ratio of average nutrient intake in NBW-RNI relative to NBW-ANI piglets. The trial lasted for 21 days. The results indicated that IUGR piglets had lower body weight and shorter CRL than NBW piglets, and weights of internal organs such as intestine, heart, liver, spleen, kidney, brain and pancreas were markedly decreased in IUGR relative to NBW piglets (P<0.01). However, the relative intestinal length, heart and brain weights to body weight were significantly higher in IUGR relative to NBW piglets (P<0.05), which implied that the programming of "trade-offs". Meanwhile, the activity of jejunal AP was markedly lower, while activity of lactase was markedly higher in IUGR relative to NBW piglets (P<0.05). The mRNA abundance of TLR-9 was markedly increased and DNA methyltransferase 1 (DNMT1) tended to increase in the ileum of IUGR relative to NBW piglets (P<0.05). Regardless of BW, RNI markedly decreased the net weight gain, ADG and ADMI of piglets (P<0.01). Moreover, the weights of heart, liver and kidney were markedly reduced by RNI (.P<0.05). Furthermore, the counts of leucocytes, lymphocytes and monocytes were significantly decreased by RNI on 28 d (P<0.05). The percentage of lymphocytes was decreased while the percentage of neutrophils increased by RNI (P<0.05). The mRNA abundances of TLR-9 and DNMT1 were significantly higher (P<0.01), while the mRNA abundances of TRAF-6 and NOD2 were significantly lower in the ileum of piglets with RNI than that of piglets with ANI (P<0.01). In summary, IUGR significantly decreased growth performance, the development of internal organs and immune function, RNI not only delayed growth performance but also impaired the immune function of piglets.Experiment 3:Effects of nucleotides supplementation on the growth performance, intestinal development and immune function of piglets withintrauterine growth restrictionThe aim of the present study was to investigate the effects of nucleotide (NT) supplementation on intestinal development and immune function of neonates with IUGR. In the present study,14 IUGR and 14 NBW piglets at 7 day of age were allocated randomly to control group (CON) or nucleotide group (NT) according to a 2×2 experimental design, which gave 7 replicates per treatment with 1 piglet per replicate. The trial lasted for 21 days. The results indicated that IUGR significantly decreased body weight, net weight gain, ADG and ADMI throughout the experimental period (P<0.01). However, there had tendency to increase in FCR of IUGR piglets during 7 and 14 days (P=0.066). Weights of internal organs such as intestine, heart, liver, spleen, kidney, pancreas and 28 day CRL and BMI were markedly decreased while the ratio of the intestinal length to weight and the ratio of intestinal weight to BW were significantly increased in IUGR relative to NBW piglets(P<0.05), which was similar with that in Experiment 2. IUGR significantly decreased the concentrations of D-xylose, IgA, IL-1β, IL-10, and the ratio of IL-1β to IL-10 (P<0.05). IUGR significantly inceased the count and percentage of neutrophils (P<0.05) while significantly decreased the percentage of lymphocytes and the percentage of spleen cells in G2+M phase (P<0.05). Moreover, IUGR decreased the villous height and villous height:crypt depth ratio in duodenum, as well as the count of gobelt cell in duodenum and jejunum (VCR) in piglets (P<0.05). The mRNA abundance of TOLLIP was decreased in the ileum of IUGR piglets relative to NBW piglets (P<0.05), meanwhile, there had tendency to decrease in the mRNA abundance of TLR-2 and TLR-9 (P<0.1). NT had tendency to increase in net weight gain and ADG throughout the experimental period (P<0.1), and significantly decreased FCR (P<0.01). NT significantly increased the concentrations of D-xylose, IgA, IL-1β and the ratio of IL-1(3 to IL-10 in serum of piglets (P<0.05). The count of leucocytes (P<0.05), lymphocytes (P<0.1) and the villous height of duodenum (P<0.05) were higher in piglet with NT diet than that with CON diet. NT significntlt increased the mRNA abundance of TLR-4, TLR-9, TOLLIP and Claudin-1 in the ileum of piglets (P<0.05). In summary, NT significantly increased the growth performance, improved intestinal development and the capability of absorbtion as well as immune function in piglets with IUGR.In these studies, together, IUGR delayed growth performance and impaired intestinal morphology and barrier as well as immune function of piglets during suckling period. Moreover, both HNI and RNI could not improve the intestinal development and immune function of IUGR piglets. However, diets supplemented with NT enhanced the growth performance, intestinal development and immune function of piglets with IUGR. |
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