| Intrauterine growth retardation (IUGR), a serious problem among human fetuses and polyembryony animals, has long-term adverse effects on fetal physiological function and metabolism. Pig fetuses are born with a high occurrence of15%to20%, and these IUGR piglets show a lower postnatal growth rate, nutrient utilization, meat quality, and health condition. In this study, IUGR piglets and piglets with normal body weight (NWB) were used to investigate the difference of body growth and development of small intestine (SI) from birth to slaughter age (160d) and study the related mechanism. Meanwhile, diet supplemented with L-arginine (Arg) and Soya lecithins (SL) were involved to evaluate the nutrition regulation of the postnatal development in IGUR piglets. This study will further provide evidences of IUGR on growth and SI development in long term and theoretical basis on research in pig production and human medicine.1Effect of IUGR on body growth in postnatal pigsForty NBW newborn piglets and forty IUGR littermates (Duroc×(Landrace×Yorkshire)) were selected to set two groups, each of which had4replicates of10pigs per replicates. The growth performance of piglets was measured. At1d,7d,21d,28d,66d, and160d of age,4pigs in each group with close body weight (BW) were chosen to slaughter and sample. The absolute and relative weight of visceral organs were weighted and calculated, the serum glucose and urea nitrogen were detected by commercial kits, the serum hormones (insulin, IGF-I, leptin, E2, and cortisol) and HSP70level were measured by commercial ELSIA kits. All data were analyzed by LSMEAN using the General Linear Model (GLM) procedures of SAS9.0. The factors of day and IUGR were involved in the statistic model. The results showed that, compared with NBW postnatal piglets, IUGR decreased (P<0.05) the BW (NBW21.26vs. IUGR15.96, SEM0.23) and ADG in postnatal piglets, as well as decreased (P<0.05) the ADFI and increased (P<0.05) the F/G in piglets from weaning to slaughter age. However, the FGR was increased (P<0.05) in IUGR piglets during1to20,1 to160, and67to160d of age by36.04%,46.51%, and28.06%, respectively, which suggested a dramatic catch-up growth. IUGR decreased (P<0.05) the serum total protein (TP) content by9.73%, enhanced (P<0.05) the serum urea nitrogen (UN) level by42.75%in postnatal piglets, which showed delayed protein metabolism and utility efficiency in IUGR postnatal piglets. The serum glucose level was not changed (P>0.05) by IUGR, however, the serum insulin level was decreased (P<0.05) by23.45%, which suggested impaired insulin secretion in postnatal IUGR piglets. In addition, IUGR decreased (P<0.05) the QUICKI, HOMA-IS, and G/I, as well as elevated (P<0.05) the HOMA-IR, these indicated that IUGR improved the insulin sensitive in IUGR postnatal piglets before mature. Compared with IUGR piglets, serum IGF-I and E2levels was decreased (P<0.05) by12.97%and18.99%in postnatal IUGR piglets. However, the serum cortisol and HSP70levels was increased (P<0.05) by24.18%and6.11%, which showed a significant stress of IUGR. In conclusion, IUGR impaired the growth and development of postnatal pigs.2Effect of IUGR on SI development in postnatal pigsThe pigs used in this part were the same as part1. The absolute and relative weight of SI and its mucosa were weighted and calculated, the SI morphological measurements were measured using a Nikon ECLIPSE80i light microscope with a computer-assisted morphometric system, the mucosal disaccharides and intestinal alkaline phosphatase (IAP) activity, the mucosal anti-oxidation capacity, the mucosal hormones (insulin, IGF-I, leptin, E2, and cortisol) and HSP70level were measured by commercial ELSIA kits, the apoptosis and proliferation of enterocytes were measured by TUNEL kits and immunohistochemistry method, and the phosphorylation of Akt, mTOR, S6K1and FoxO4in SI mucosa were evaluated by Western Blot. All data were analyzed as described in part1. The results showed that, In postnatal piglets, IUGR decreased (P<0.05) the weight of SI by30.07%, mucosa by28.75%, and non-mucosa by30.53%, as well as the intestinal and mucosal weight per length of SI. This showed that IUGR impaired the growth and development of SI, and the adverse effect was persistent up to66d of age at least. The TMT, VH, HWR, VCR and VS of duodenum, proximal and distal jejunum, and ileum were decreased (P<0.05) by IUGR in postnatal piglets. The impaired structure of SI induced by IUGR continued to160d of age at least. IUGR impaired the enzymes mature in SI, the activity of mucosal lactase (-20.31%), maltase (-30.73%), and IPA (-23.74%) was decreased (P<0.05) by IUGR in postnatal piglets. IUGR increased (P<0.05) the content of mucosal MDA (26.98%) and H2O2(12.68%), as well as decreased (P<0.05) the T-AOC (-17.28%), GPx (-17.22%), and SOD (-11.62%), which showed a severe oxidant stress (OS). IUGR also impaired (P<0.05) the activity of NOS (-15.00%), and reduced (P<0.05) the content of NO (-22.16%) in SI mucosa of postnatal piglets. The IHC staining of HSP70showed that, the expression of HSP70was increased in broken villi. ELISA result showed that IUGR increased (P<0.05) the mucosal HSP70content during suckling period and early time after weaning, which HSP70represented the adaptation reaction. However, the content of HSP70was lower (P<0.05) in IUGR piglets compared with NBW piglets at66and160d of age, which HSP70may indicate the capacity of anti-stress. IUGR decreased (P<0.05) the proliferation index (PI) of enterocytes by6.29%, increased (P<0.05) the apoptosis index (AI) by46.06%, AI/PI by52.06%, as well as the mucosal Caspase-3relative activity by14.11%in postnatal piglets. This indicated that, IUGR changed the homeostasis between proliferation and apoptosis of enterocytes, which could impair the structure and growth of SI. The concentration of mucosal insulin (-31.34%), IGF-I (-25.73), and E2(-11.58%) was decreased (P<0.05) by IUGR in postnatal period. Compared with NBW piglets, the phosphorylation of mucosal Akt, mTOR, S6K1, and FoxO4was also reduced (P<0.05) in IUGR piglets by49.49%,31.27%,49.10%, and50.81%, respectively. These indicated that the Akt and mTOR signaling were involved in regulating SI development. In addition, the mucosal E2/Akt/FoxO4pathway might play important roles on SI development in piglets at66and160d of age. In conclusion, IUGR delayed the growth and intestinal development of postnatal piglets. These may due to the decreased growth factors secretion, mucosal Akt, mTOR, and FoxO4activity, as well as imbalanced enterocytes apoptosis and proliferation.3Dietary supplementation with Arg and SL on body growth and SI development in suckling IUGR pigletsA total of twenty-four piglets including six NBW piglets and eighteen IUGR piglets were selected. All piglets were weaned at7d of age. Then they were assigned equally to four groups:six NBW (Group NBW) and six IUGR piglets fed control diet (Group IUGR), six IUGR piglets fed Arg diet supplemented with0.60%Arg (Group IUGR+Arg), and six IUGR piglets fed Arg diet supplemented with1.50%SL (Group IUGR+SL), respectively from7to14d of age. All piglets were housed individually in plastic floored pens and free access to water. At14d of age,4pigs in each group with close BW were chosen to slaughter and sample. The content of serum AA was measured by HPLC. Other parameters measured were the same as part1. Data were analyzed by LSMEAN using the GLM procedures of SAS9.0. The results showed that,(1) Dietary supplementation with0.60%Arg in IUGR piglets increased (P<0.05) the14d BW by21.78%, the ADG by47.30%and DMI by21.41%, and decreased (P<0.05) the diarrhea rate by61.46%compared with IUGR piglets fed control diet. However, the14d BW of piglets in IUGR+Arg group was still lower (P<0.05) than that of IUGR piglets. In IUGR piglets, Arg decreased (P<0.05) serum cortisol and HSP70level, and mucosal HSP70content, which indicated a reduced stress effect. Compared with IUGR piglets, diet supplemented by Arg increased (P<0.05) the serum and mucosal concentration of Arg, Orn, Cit, and Pro, the activity of NOS and the content of NO, the level of insulin, and decreased (P<0.05) the serum urea nitrogen in IUGR piglets at14d of age. However, the level of glucose, TP, IGF-I, leptin and E2was not changed (P>0.05) by Arg in IUGR piglets.In group IUGR+Arg, the weight of SI, its mucosa and non-mucosa, as well as SI weight/length was higher (P<0.05) than that of IUGR piglets. The activity of mucosal lactase and maltase was also elevated (P<0.05) by Arg in IUGR piglets. Arg reduced the content of MDA, and increased the T-AOC and GPx of SI mucosa in IUGR piglets, which suggested improved the anti-oxidation of SI. Arg treated improved the structure of SI in IUGR piglets. The VH of jejunum and ileum, the TMR and HWR of ileum was increased by Arg in IUGR piglets at14d of age.Dietary supplementation with Arg increased (P<0.05) the mucosal insulin, IGF-I, as well as the phosphorylation of Akt by47.09%and mTOR by60.34%compared with IUGR piglets. Meanwhile, Arg treated decreased (P<0.05) the AI and AI/PI by42.86%and44.08%, respectively, but did not affect the PI (P>0.05).(2) Dietary supplementation with SL in IUGR piglets during suckling period increased (P<0.05) the14d BW and ADG by20.46%and53.32%compared to IUGR piglets. However, the DMI was not changed (P>0.05) by SL supplementation, this indicated that SL improved the growth of IUGR piglets may via increasing the nutrients utility. Similarly as Arg supplementation, SL decreased (P<0.05) the serum cortisol and HSP70levels to reduce IUGR induced stress, increased (P<0.05) the mucosal T-AOC, GPx, and SOD levels and decreased (P<0.05) the content of MDA to relieve OS. The activity of mucosal lactase and maltase was also increased (P<0.05) by SL in IUGR piglets. Compared with IUGR control piglets, dietary supplementation with SL enhanced (P<0.05) the signaling of Akt and mTOR by38.84%and36.12%, reduced (P<0.05) the AI by24.34%in IUGR piglets. However, the enterocytes PI, mucosal Caspase-3relative activity, AA concentrations, insulin and IGF-I level were not changed by SL supplemented in IUGR piglets. This suggested that the regulation mechanism of SL on body growth and SI development in IUGR piglets differed from Arg supplementation.Conclusion, diet supplemented with Arg and SL increased the body and intestinal tissue grow, improved the morphology and function of SI. The elevated insulin level, Akt and mTOR activity, and decreased enterocytes apoptosis contributed to these benefit effects.4Diet supplemented with SL on body growth and SI development in weaning pigletsAt the time of birth, sixteen NBW piglets and thirty-two IUGR piglets were selected. All piglets were weaned at21d of age. Then they were assigned equally to three groups:16NBW (Group NBW) and16IUGR piglets fed control diets (Group IUGR), and16IUGR piglets fed Arg diet supplemented with1.50%SL (Group IUGR+SL), respectively from21to160d of age. Each groups had4replicates of4pigs per replicates. All piglets were housed by replicate with ad libitum feeding and drinking. At28d,66d, and160d of age,4pigs in each group with close BW were chosen to slaughter and sample. The indexes measured were the same as part1. Data were analyzed by LSMEAN using the GLM procedures of SAS9.0. The factors of day and SL were involved in the statistic model. The results showed that,(1) Dietary supplementation with SL increased (P<0.05) the growth performance, improved the catch-up growth. The BW of IUGR+SL piglets at160d of age was not different (P<0.05) from that of NBW piglets. The level of serum insulin and E2was increased by SL in IUGR piglets after weaning. The increased insulin in IUGR+SL piglets was consistent with the increased serum glucose. The serum cortisol level was decreased (P<0.05) by SL supplementation in IUGR piglets after weaning. However, the serum and mucosal HSP70level was increased (P<0.05), which may indicated that SL improved the immune function and anti-stress capacity.(2) Similarly as the regulation effect on SI of IUGR piglets during suckling period, SL supplemented improve the SI growth, increased (P<0.05) the activity of lactase, maltase and IAP, reduced the OS. However, the NO and NOS were not changed by SL in IUGR piglets after weaning. Dietary supplementation with SL increased (P<0.05) the activity of Akt, reduced (P<0.05) the enterocytes AI, increased (P<0.05) the VH, TMT and VS of SI. However, the mTOR and FoxO4activity was not change by SL supplementation in IUGR piglets after waning.In conclusion, diet supplemented with SL in weaning piglets improved the body growth and intestinal development. These were closely related to the elevated Akt signal transduction and decreased enterocytes apoptosis. |
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