Dietary bile acid supplementation in weaned piglets with intrauterine growth retardation improves colonic microbiota,metabolic activity,and epithelial function

Background Intrauterine growth retardation(IUGR)is one of the major constraints in animal production.Our previ-ous study showed that piglets with IUGR are associated with abnormal bile acid(BA)metabolism.This study explored whether dietary BA supplementation could improve growth performance and colonic development,function,micro-biota,and metabolites in the normal birth weight(NBW)and IUGR piglets.A total of 48 weaned piglets(24 IUGR and 24 NBW)were allocated to four groups(12 piglets per group):(i)NBW group,(ii)NBW+BA group,(iii)IUGR group,and(iv)IUGR+BA group.Samples were collected after 28 days of feeding.Results The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio,while decreased the plasma diamine oxidase(DAO)concentration in the NBW pig-lets(P<0.05).Dietary BA supplementation to IUGR piglets decreased(P<0.05)the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin,suggesting a beneficial effect on epithelial integrity.Moreover,dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance(P<0.05),whereas Lactobacillus was the dominant genus in the colon.Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA,respectively,which was associated with the colonic function of IUGR piglets.Furthermore,dietary BA supplementation to IUGR piglets upregulated the expressions of CAT,GPX,SOD,Nrf1,IL-2,and IFN-γin colonic mucosa(P<0.05).Conclusions Collectively,dietary BA supplementation could improve the colonic function of IUGR piglets,which was associated with increasing proportions of potentially beneficial bacteria and metabolites.Furthermore,BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.

Pterostilbene attenuates intrauterine growth retardation-induced colon inflamm tion in piglets by modulating endoplasmic reticulum stress and autophagy

Background:Endoplasmic reticulum(ER)stress and autophagy are implicated in the pathophysiology of intestinal inflammation;however,their roles in intrauterine growth retardation(IUGR)-induced colon inflammation are unclear.This study explored the protective effects of natural stilbene pterostilbene on colon inflammation using the IUGR piglets and the tumor necrosis factor alpha(TNF-α)-treated human colonic epithelial cells(Caco-2)by targeting ER stress and autophagy.Results:Both the IUGR colon and the TNF-α-treated Caco-2 cells exhibited inflammatory responses,ER stress,and impaired autophagic flux(P<0.05).The ER stress inducer tunicamycin and the autophagy inhibitor 3-methyladenine further augmented inflammatory responses and apoptosis in the TNF-α-treated Caco-2 cells(P<0.05).Conversely,pterostilbene inhibited ER stress and restored autophagic flux in the IUGR colon and the TNF-α-treated cells(P<0.05).Pterostilbene also prevented the release of inflammatory cytokines and nuclear translocation of nuclear factor kappa B p65,reduced intestinal permeability and cell apoptosis,and facilitated the expression of intestinal tight junction proteins in the IUGR colon and the TNF-α-treated cells(P<0.05).Importantly,treatment with tunicamycin or autophagosome-lysosome binding inhibitor chloroquine blocked the positive effects of pterostilbene on inflammatory response,cell apoptosis,and intestinal barrier function in the TNF-α-exposed Caco-2 cells(P<0.05).Conclusion:Pterostilbene mitigates ER stress and promotes autophagic flux,thereby improving colon inflammation and barrier dysfunction in the IUGR piglets and the TNF-α-treated Caco-2 cells.

Intrauterine growth retardation affects liver bile acid metabolism in growing pigs:effects associated with the changes of colonic bile acid derivatives

Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon.However,the consequences of IUGR on bile acid metabolism in pigs remained unclear.The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of grow-ing pigs with IUGR using bile acid targeted metabolomics.Furthermore,we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight(NBW)pigs at different growth stages that were 7,21,and 28-day-old,and the average body weight(BW)of 25,50,and 100 kg of the NBW pigs.Results:The results showed that the plasma total bile acid concentration was higher(P<0.05)at the 25 kg BW stage and tended to increase(P=0.08)at 28-day-old in IUGR pigs.The hepatic gene expressions related to bile acid synthe-sis(CYP7A1,CYP27A1,and NTCP)were up-regulated(P<0.05),and the genes related to glucose and lipid metabolism(ATGL,HSL,and PC)were down-regulated(P<0.05)at the 25 kg BW stage in IUGR pigs when compared with the NBW group.Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs.The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased(P<0.05),while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased(P<0.05)in IUGR pigs,when compared with the NBW pigs at the 25 kg BW stage.Moreover,Spearman’s correlation analysis revealed that colonic Unclassified_[Mogi-bacteriaceae],Lachnospira,and Slackia abundances were negatively correlated(P<0.05)with dehydrolithocholic acid,as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage.Conclusions:These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs,especially at the 25 kg BW stage,these effects being paralleled by a modification of bile acid derivatives concentra-tions in the colonic content.The plausible links between these modified parameters are discussed.

Effect of early nutrition on intestine development of intrauterine growth retardation in rats and its correlation to leptin

AIM：To investigate the intestine and body development of intrauterine growth retardation（IUGR）rats under early different protein diet and to analyze the correlation between leptin and intestine and body development．METHODS：An IUGR rat model was established by food restriction of pregnant female rats．Fifty-six neonatal IUGR rats and 24 neonatal normal rats were randomly divided into normal control group（Cgroup），IUGR model group （scgroup），low protein diet IUGR group（SL group），and high protein diet IUGR group（SH group）．Eight rats were killed per group at wk 0，4，and 12．Serum leptin，body weight（BW），body length（BL），intestinal weight（IW），intestinal length（IL），andintestinal disaccharidase（including lactase，maltase，and saccharase） were detected．RESULTS：BW（4．50±0．41g），BL（5．96±0．40cm），IW（0．05±0．01g），and IL（15.9±2．8cm）in neonatal IUGR rats were much lower than those in Cgroup（6．01±0．55g，6．26±0．44cm，0．10±0．02g，21.8±2．7cm，P〈0．05），while intestinal lactase and maltase activities were higher than those in Cgroup．SH group showed the fastest catch up growth and their BW，BL，IW，and IL reached the Cgroup level at wk 4．SC group showed relatively slower catch up growth than SH group，and their BW，BL，IW did not reach the Cgroup level at wk 4．SL group did not show intestine and body catch up growth．Intestinal maltase [344±33μmol／（min·q）]and saccharase activities[138±32μmol／（min·g）]in SL group were both markedly lower than nose in C group [751±102，258±271μmol／（min·g），P〈0．05]．There were no significant difierences in lactase activities at wk 4 and disaccharidase activities at wk 12 among all groups（P〈0．05）．The leptin level in SL group（0．58±0．12ng／mL） was the highest in all groups，and much lower in SH group（0．21±0．03ng／mL） than that in any other IUGR groups at wk 4（P〈0．05）．Leptin was negatively related to BW （r=-0．556，P=0．001），IW（r=-0．692，P=0．001） and IL（r=-0．738，P=0．000）at wk 4，while no correlation was found at wk 12．CONCLUSION：High protein diet is a reasonable early nutritional mode to IUGR rats in promoting intestine and body catch up growth．

Effect of Dietary Folic Acid Supplementation on Growth Performance and Hepatic Protein Metabolism in Early-Weaned Intrauterine Growth Retardation Piglets

To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation （IUGR） piglets, 24 male （Durocx （LandracexYorkshire）） weaned （14-d-old） IUGR piglets were randomly divided into 3 treatments with 8 replicates of 1 piglet per replicate. The piglets in each treatment were fed basal diet supplementation with either 0 （control）, 5 and 10 mg kg^-1 folic acid. The trial lasted for 21 d. Dietary folic acid supplementation reduced average daily feed intake （ADFI） （P〈0.05）. In addition, the average daily gain （ADG） in 10 mg kg^-1 folic acid group was significantly decreased （P〈0.01） and the ratio of feed：gain （F/G） increased slightly （P〉0.05）. Serum folic acid concentration increased （P〈0.01） with increasing folic acid inclusion, however, serum homocysteine concentration decreased significantly （P〈0.01）. Enhanced serum urine nitrogen （SUN） and diminished serum total protein （TP） as well as liver TP content were observed in 10 mg kg^-1 folic acid group （/＇〈0.05）. Furthermore, the relative mRNA expressions of insulin-like growth factor 1 （IGF-1） and mammalian target of rapamycin （m-TOR） in liver were respectively tended to reduce （P=0.06） and significantly downregulated （P〈0.05） in 10 mg kg1 group, in compared with 5 mg kg1 group. However, when compared with control group, folic acid supplementation had no significant effect on the mRNA abundance of IGF- 1 and m-TOR. The results indicated that supplementation with 10 mg kg-I folic acid impaired growth performance and hepatic protein metabolism of early-weaned IUGR piglets while 5 mg kg-~ folic acid enriched diet exerted limited positive effects.

INTRAUTERINE GROWTH RETARDATION AT FULL TERM PREGNANCIES WITH ENDOCRINE FACTORS

Objective To investigate the relationship between intrauterine growth retardation (IUGR) and endocrine parameters so as to assess the effects or the main endocrine ractors on IUGR. The concentrations of growth hormone(GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum.Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants’ weight were taken as control. Growth hormone and insulin were measured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentrations of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH4. 63μ/L vs 7. o1μg/L, insulin 1o. 68μIU/ml vs 31. 44μIU/ml, T487. 39nmol/L vs 138. 1onmol/L. P <o. o5, o. o5 and o. o5, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (1o. 84μmIU/L vs 5. 75μmIU/L, P <o. o1 ). The concentration of growth hormone in maternal serum and the concentration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1. 77μg/L vs 2. 74μg/L,P <o. o1, insulin 5. 84μIU/ml vs 15. 64μIU/ml, P <o. o1). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relatlve scarcity of growth hormone and insulin seems to be a factor to compromise the fetus’ metabolism. Besides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.

EFFECTS OF EARLY NUTRITION INTERVENTION ON IGF1, IGFBP3,INTESTINAL DEVELOPMENT, AND CATCH-UP GROWTH OF INTRAUTERINE GROWTH RETARDATION RATS

To investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1),insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet. Methods IUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group(S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week. Results (1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF-1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length. Conclusions The serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the ab-sorption of nutrition

Resveratrol and its derivative pterostilbene ameliorate intestine injury in intrauterine growth-retarded weanling piglets by modulating redox status and gut microbiota

Background:Intestinal disorder is an important factor contributing to growth lag and high rates of morbidity and mortality of piglets with intrauterine growth retardation(IUGR).Resveratrol(RSV)and its derivative pterostilbene(PT)are natural stilbenes possessing various bioactivities,such as antioxidative and anti-inflammatory effects.This study compared the protective potential of RSV and PT on the intestinal redox status and gut microbiota in weanling piglets with IUGR.Methods:Eighteen male piglets of normal body weight(NBW)and 54 same-sex IUGR piglets were chosen according to their birth and weaning weights.The NBW piglets accepted a basal diet,while the IUGR piglets were allotted to one of three groups according to their body weight at weaning and received a basal diet,an RSV-supplemented diet(300 mg/kg),or a PT-supplemented diet(300 mg/kg),respectively.Results:Compared with IUGR piglets,both RSV and PT improved the IUGR-associated decrease in jejunal villus height and increases in plasma diamine oxidase activity and D-lactate level and jejunal apoptosis of piglets(P<0.05).Administering RSV and PT also enhanced jejunal superoxide dismutase activity and the mRNA and protein expression of superoxide dismutase 2 of IUGR piglets by promoting nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation(P<0.05).Comparatively,PT was more effective than RSV in elevating the villus height/crypt depth ratio and occludin mRNA and protein levels in the jejunum of IUGR piglets(P<0.05).PT was also superior to RSV in increasing Nrf2 nuclear translocation and inhibiting malondialdehyde accumulation in the jejunum of IUGR piglets(P<0.05).Additionally,RSV modulated the composition of cecal microbiota of IUGR piglets,as evidenced by increasing the prevalence of the phylum Bacteroidetes and the genera Prevotella,Faecalibacterium,and Parabacteroides and inhibiting the growth of the phylum Proteobacteria and its genera Escherichia and Actinobacillus(P<0.05).Moreover,RSV significantly increased the butyrate concentration in the cecum of IUGR piglets(P<0.05).Conclusion:PT is more potent than RSV to prevent intestinal oxidative stress,while RSV has a stronger capacity to regulate gut microbiota compared to PT.

Restored intestinal integrity,nutrients transporters,energy metabolism,antioxidative capacity and decreased harmful microbiota were associated with IUGR piglet's catch-up growth before weanling

Background:Intrauterine growth restriction(IUGR)is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth(CUG)before weanling could significantly restore this negative influence.But there was limited knowledge about the underlying mechanism of CUG occurrence.Methods:Eighty litters of newborn piglets were divided into normal birth weight(NBW)and IUGR groups according to birth weight.At 26 d,those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG,and the piglets with IUGR still below average body weight were considered as NCUG.This study was conducted to systemically compare the intestinal difference among NBW,CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth.Results:The results indicated that the m RNA expression of nutrients(amino acids,glucose,and fatty acids)transporters,and mitochondrial electron transport chain(ETC)I were upregulated in CUG piglets'gut with improved morphology compared with those NCUG,as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism.Meanwhile,CUG piglet's gut showed higher antioxidative capacity with increased SOD and GSHPx activity,decreased MDA levels,as well as higher m RNA expressions of Nrf2,Keap1,SOD,and GSH-Px.Furthermore,inflammatory parameters including TNF-α,IL-1β,IL-6,and IL-12 factors,and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine,while the protein expression of ZO-1,Occludin and Claudin-1 was reduced.The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets,and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets.Conclusions:CUG piglet's intestine showed comprehensive restoration including higher nutrients transport,energy metabolism,antioxidant capacity,and intestinal physical barrier,while lower oxidative stress,inflammatory response,and pathogenic microbiota.

Effects of Maternal Folic Acid Supplementation on Hepatic Apoptosis-Related Gene Expressions between Intrauterine Growth Restriction and Normal Body Weight Piglets

Intrauterine growth retardation （IU- GR） causes significantly negative effects on the meth- ylation status of genes related to cell apoptosis com- pared with normal body weight （NBW） piglets. Thus, the objective of the present study was to exam- ine the effects of maternal dietary folic acid supple- mentation on genes expression profile for hepatic ap- optosis in IUGR and NBW piglets. Twenty four York- shire gilts were allocated randomly to one of the two diets ： control （ C, folic acid 1.3 mg/kg） or folic acid supplementation （ FS, folic acid 30 mg/kg） after mat- ing. Gene expressions in liver samples were deter- mined and revealed that the mRNA expressions of p53 ,BCL-2 associated X protein （Bax）, and Cyclin- dependent kinase inhibitor 1A （CDKN1A） were up-regulated in IUGR piglets compared with NBW pig- lets fed C diets,but could be reversed by maternal fo- lic acid supplementation. The expressions of vascular endothelial growth factor （VEGF）, Serine-protein Ki- nase-Ataxia Telangiectasia Mutated （ATM） ,and Cad- herin-associated protein-beta-catenin 1 （ CTNNB1 ） were influenced by maternal folic acid supplementa- tion significantly, but were not influenced by birth weight. Expression of p53 binding protein-MDM-2 （ MDM-2 ） remained unchanged. In conclusion, these results demonstrated that maternal folic acid supple- mentation could exert positive effects on genes related to apoptosis in IUGR and NBW piglets, which might facilitate their postnatal health and growth perform- alice.

Supplementation with dimethylglycine sodium salt improves lipid metabolism disorder in intrauterine growth-retarded pigs

This study aims to elucidate the mechanism of lipid metabolism disorder in intrauterine growth retardation(IUGR)pigs and the potential alleviating effects of dimethylglycine sodium salt(DMG-Na).A total of 60 male newborn piglets were selected for this study.Within each litter,one normal birth weight(NBW)male piglet(1.53±0.04 kg)and two IUGR male piglets(0.76±0.06 kg)were chosen based on their birth weight.The piglets were divided into three groups for the study:NBW pigs received a PBS gavage and a common basal diet(NBW-C group),IUGR pigs received the same PBS gavage and common basal diet(IUGR-C group),and IUGR pigs received a 70-mg DMG-Na gavage along with a common basal diet supplemented with 0.1%DMG-Na(IUGR-D group).At 150 d of age,all piglets underwent euthanasia by exsanguination following electrical stunning,after which plasma,liver,and longissimus dorsi(LM)samples were promptly collected.The IUGR-D group demonstrated improvements in plasma parameters(P<0.05),with lower triglyceride and free fatty acid(FFA)values,and hormone levels(P<0.05),with lower growth hormone,insulin,and homeostasis model assessment of insulin resistance values.Restoration of lipid metabolism was observed(P<0.05),with lower triglyceride and FFA,and higher hepatic lipase and total lipase values in the liver,and lower triglyceride and FFA values in the LM.Mitochondrial ETC complexes showed increased levels(P<0.05),including higher complex III values in the liver,and higher complex I,complex III,and complex V values in the LM.Enhanced levels of energy metabolites were noted(P<0.05),with higher NAD^(+),NAD^(+)/NADH,adenosine triphosphate,and mtDNA values,and lower NADH values in the liver and LM.Additionally,meat quality parameters showed improvement(P<0.05),with higher pH 24 h and a^(*)values,and lower drip loss 48 h,L^(*),and b^(*)values.The expressions of lipid metabolism and mitochondrial function-related genes and proteins were upregulated(P<0.05)compared to the IUGR-C group.In conclusion,it was indicated that IUGR pigs experienced lipid metabolism disorders and diminished performance.However,supplementation with DMG-Na showed promise in mitigating these adverse physiological effects by safeguarding body tissues and modulating energy metabolism.

Dietary dihydroartemisinin supplementation alleviates intestinal inflammatory injury through TLR4/NOD/NF-kB signaling pathway in weaned piglets with intrauterine growth retardation

The aim of present study was to evaluate whether diets supplemented with dihydroartemisinin(DHA)could alleviate intestinal inflammatory injury in weaned piglets with intrauterine growth retardation(IUGR).Twelve normal birth weight(NBW)piglets and 12 piglets with IUGR were fed a basal diet(NBW-CON and IUCR-CON groups),and another 12 piglets with IUGR were fed the basal diet supplemented with DHA at 80 mg/kg(IUGR-DHA group)from 21 to 49 d of age.At 49 d of age,8 piglets with similar body weight in each group were sacrificed.The jejunal and ileal samples were collected for further analysis.The results showed that IUGR impaired intestinal morphology,increased intestinal inflamma-tory response,raised enterocyte apoptosis and reduced enterocyte proliferation and activated trans-membrane toll-like receptor 4(TLR4)/nucleotide-binding and oligomerization domain(NOD)/nuclear factor-kB(NF-kB)signaling pathway.Dihydroartemisinin inclusion ameliorated intestinal morphology,indicated by increased villus height,villus height-to-crypt depth ratio,villus surface area and decreased villus width of piglets with IUGR(P<0.05).Compared with NBW piglets,IUGR piglets supplemented with DHA exhibited higher apoptosis index and caspase-3 expression,and lower proliferation index and proliferating cell nuclear antigen expression in the intestine(P<0.05).Dihydroartemisinin supple-mentation attenuated the intestinal inflammation of piglets with IUGR,indicated by increased concen-trations of intestinal inflammatory cytokines and lipopolysaccharides(P<0.05).In addition,DHA supplementation down-regulated the related mRNA expressions of TLR4/NOD/NF-kB signaling pathway and upregulated mRNA expressions of negative regulators of TLR4 and NOD signaling pathway in the intestine of piglets with IUGR(P<0.05).Piglets in the IUGR-DHA group showed lower protein ex-pressions of TLR4,phosphorylated NF-kB(pNF-kB)inhibitorα,nuclear pNF-kB,and higher protein expression of cytoplasmic pNF-kB in the intestine than those in the IUGR-CON group(P<0.05).In conclusion,DHA supplementation could improve intestinal morphology,regulate enterocyte prolifera-tion and apoptosis,and alleviate intestinal inflammation through TLR4/NOD/NF-kB signaling pathway in weaned piglets with IUGR.

早期营养干预改善IUGR大鼠胰岛素抵抗及其与血清瘦素的关系

【目的】探讨生后早期不同饮食构成喂养对宫内生长迟缓(IUGR)大鼠胰岛素抵抗的远期影响及其与瘦素、腹部内脏脂肪的相关关系。【方法】IUGR新生雌鼠48只和正常新生雌鼠10只随机分为5组予下述相应饮食饲料喂养母鼠3周:①IUGR模型组(S/N组)予常规饮食,②IUGR高碳水化合物饮食组(A组),③IUGR高脂肪饮食组(B组),④IUGR高蛋白质饮食组(C组)⑤正常对照组(C/N组)予常规饮食。第4周起各组幼鼠断乳后均予常规饮食饲料喂养至实验结束。各组大鼠于12周(成年期)分别测定体质量、肾周脂肪质量(肾脂)、血清瘦素、血糖、胰岛素并计算胰岛素敏感指数(ISI)、胰岛素抵抗指数(IRI)。【结果】12周时IUGR模型组大鼠肾脂增多,血清瘦素和IRI升高、ISI下降(P<0.05)。IUGR高蛋白饮食组体质量(242.6±17.5)g虽高于C/N组(192.1±37.2)g,但与S/N组(213.4±27.3)g比较无显著性差异(P>0.05),且不伴肾脂(1.46±0.67)g增多,血清瘦素(0.43±0.26)μg/L、ISI(4.47±0.45)和IRI(0.78±0.45)也与正常对照组(1.41±0.42)g,(0.42±0.34)μg/L,4.46±0.42和0.77±0.31比较差异无统计学意义(P>0.05)。【结论】生后哺乳期给予高蛋白质饮食早期营养干预然后恢复正常饮食,可使IUGR大鼠既能达到体格追赶生长。

早期营养对IUGR大鼠糖耐量和胰岛素敏感性的远期影响

【目的】了解宫内发育迟缓(IUGR)和生后早期蛋白质营养不良对IUGR大鼠糖耐量和胰岛素敏感指数(ISI)及胰岛素抵抗指数(IRI)的远期影响。【方法】采用被动吸烟法制作IUGR大鼠动物模型,新生正常鼠仔102只和IUGR鼠仔105只随机分为4组:①正常对照组;②IUGR模型组;③正常大鼠低蛋白饮食组(CLP组);④IUGR大鼠低蛋白饮食组(SLP组)。观察各组大鼠在生后4周(幼年期)、12周(成年期)和48周龄(老年期)时糖耐量和胰岛素释放试验变化。【结果】①SLP组大鼠宫内发育迟缓和生后早期蛋白质营养不良其远期葡萄糖-胰岛素代谢功能受损明显,至48周时空腹血糖(5.2±1.4)mmol/L已升高,胰岛素(31. 2±3.4)mU/L水平明显升高,ISI(1.7±0.4)明显下降,IRI(8.7±1.8)明显升高,与正常对照组[(4.5±1.1)mmol/L,(12.9±1.0)mU/L和2.8±0.2,2.3±0.41比较均有显著性差异(P<0.05或P<0.01)。②CLP组大鼠生后早期单纯蛋白质营养不良的远期影响主要表现为糖负荷后胰岛素对血糖升高的应答分泌反应延迟和糖耐量减低。③IUGR模型组大鼠生后即给予正常营养供给,其葡萄糖-胰岛素代谢紊乱的程度减轻,但仍有糖耐量减低。【结论】在宫内和/或生后早期机体发育的关键时期,蛋白质营养不良将对葡萄糖-胰岛素代谢功能产生长期的不良影响。

Clinical Study on Effect of Chinese Herbal Medicine for Supplementing Kidney and Qi and Activating Blood Circulation in Treating Intrauterine Growth Retardation of Fetus

Objective: To explore the therapeutic effect and the possible working mechanism in using Chinese herbal medicine (CHM) for supplementing Kidney and Qi, and activating blood circulation in treating intrauterine growth retardation of fetus (IUGR). Methods: Fifty-five cases of IUGR were divided into two groups, 30 cases in the CHM group treated with CHM and the 25 in the control group treated with amino acids. The effect of CHM treatment was observed and compared with that of the control group, normal pregnancy group and non-treated IUGR group. Results: Body weight of the newborns in the CHM was markedly higher than that in the control group. Not only the maternal fundal height (FH) and the abdominal circumference (AC), but also the fetal growth parameters, including biparietal diameter, head circumference (HC), and femur length (FL) in the CHM group increased much faster than those in the control group. After CHM treatment, the maternal serum levels of estriol (E3) and human placental lactogen (hPL) approached to those in the normal pregnancy group, but the control group,in comparison with the normal pregnancy group, was significantly different. The umbilical venous plasma concentration of essential amino acids in both treated groups improved, but the improvement in the CHM group was more significant than that in the control group. No apparent adverse effect of CHM was observed in either mother or fetus.Conclusion: CHM for supplementing Kidney and Qi and activating blood circulation was more effective in improving placental function and enhancing amino acid transportation than amino acid

被动吸烟法建立IUGR动物模型

将新西兰兔分为三组,A组:整个孕期被动吸烟:B组:孕后半期被动吸烟;C组:对照组,结果A、B两组母兔体重增加(分别为0.65kg及0.85kg)较对照组(1.18kg)少;胎仔的体重、肝、脑重量及胎盘重量均较对照组轻,其中以体重及肝脏重量相差更明显(P<0.001):吸烟两组的子宫胎盘血流量与对照组比较明显减少(P<0.001):吸烟两组IUGR发生率(分别为48.33%及20.37%)较对照组(3.45%)明显增加(分别为P<0.0001、P<0.05).整个孕期被动吸烟的孕兔可产生混合型IUGR动物模型,孕后半期被动吸烟则产生不对称型IUGR动物模型。

宫内发育迟缓仔猪断奶后肠道菌群特征及其与生长的潜在联系

本试验旨在研究正常体重(NBW)仔猪和宫内发育迟缓(IUGR)仔猪肠道菌群的定植特征及其与器官生长发育的潜在联系。试验选取NBW仔猪和IUGR仔猪各12头,21日龄断奶后转至单栏饲喂,经7 d适应后,开始为期28 d的饲养试验。分别于试验的第0和28天空腹称重并记录,屠宰后分离肝脏、脾脏和胰腺称重;分离空肠、回肠和结肠称重并测量长度,采集肠内容物进行微生物组分析。结果表明,与NBW仔猪相比,IUGR仔猪的末重、肝脏重、空肠重和长度均显著降低(P<0.05),而肝脏系数,回肠重、长度和系数以及结肠重、长度与系数均显著升高(P<0.05)。NBW仔猪和IUGR仔猪空肠、回肠和结肠微生物α和β多样性均无明显改变,而IUGR仔猪空肠变形菌门(Proteobacteria)丰度呈升高趋势(P=0.08),回肠Proteobacteria和放线菌门(Actinobacteria)丰度显著升高、厚壁菌门(Firmicutes)丰度显著降低(P<0.05)。此外,Spearman分析发现肠道菌丰度与仔猪器官发育密切相关,其中呈显著负相关(P<0.05)的包括:空肠葡萄球菌属(Staphylococcus)与末重、肝脏重和胰腺重,回肠Firmicutes与回肠重、回肠长度和回肠系数;呈显著正相关(P<0.05)的包括:回肠Proteobacteria与回肠重、回肠系数和肝脏系数,结肠Actinobacteria与结肠重和结肠系数。由上可见,NBW仔猪与IUGR仔猪断奶后肠道菌群定植发生明显变化,这与仔猪的器官生长发育受阻具有明显的相关性。

IUGR大鼠胰岛素样生长因子与小肠及体格发育关系的研究

目的 生后早期的生长主要受营养的调控 ,营养物质 胰岛素 胰岛素样生长因子 (IGF)轴在胎儿宫内发育迟缓 (IUGR)生长追赶及胃肠发育中起着重要的作用 ,而胃肠发育又与营养物质的吸收、生长追赶关系密切。目前国内有关IUGR出生时小肠发育状况报道甚少 ,且仅限于IUGR出生时胃肠形态结构的观察。该研究探讨生后早期不同蛋白质和热卡水平的营养干预如何调控IGF系统及影响IUGR大鼠的小肠发育和体格生长追赶 ,并追踪至成年期。方法 采用孕母饥饿法建立IUGR模型。 6 4只IUGR新生鼠随机分为 4组 :IUGR正常饮食组(SC组 ) ,饮食中蛋白含量 2 0 % ;IUGR高蛋白组 (SH组 ) ,饮食中蛋白含量占 30 % ;IUGR低蛋白组 (SL组 ) ,饮食中蛋白含量为 1 0 % ;IUGR高热卡组 (SA组 ) ,饮食中热卡较其它组高 2 0 %。 1 6只正常新生鼠为正常对照组 (C组 )予以正常饮食。幼鼠 3周断乳后继续予原饮食模式 1周 ,第 4周起各组均予正常饮食喂养。分别于出生时及生后第4周、1 2周测定各组大鼠的血清IGF 1、胰岛素生长因子结合蛋白 3(IGFBP 3)浓度及体重、身长和小肠重量、长度。结果 IUGR大鼠虽然宫内营养不良 ,但SH组及SA组呈快速小肠发育和体格生长追赶伴IGFs水平明显升高 ,其中 4周时SH组IGFs水平显著高于其余各组 (P <0 .0 5 ) ;

新生IUGR大鼠脑内胰岛素信号通路相关蛋白表达的变化

目的研究宫内发育迟缓(IUGR)大鼠脑内胰岛素信号通路相关蛋白及突触后致密区蛋白(PSD95)表达的变化,探讨神经变性病可能的发育起源机制。方法应用热量限制法建立IUGR大鼠模型,通过RT-PCR和Western blot方法检测新生IUGR仔鼠脑内胰岛素受体(InsR)、磷酸化InsR,胰岛素受体底物-1(IRS-1)及PSD95的表达水平。采用SPSS11.5软件进行统计分析。结果与对照组相比,IUGR新生仔鼠体质量和脑质量均显著降低(P<0.01),但脑质量/体质量比值却明显增加(P<0.01);脑内InsR在mRNA水平表达减少(P<0.05);在蛋白质水平InsRα和β亚基表达减少(P<0.05,P<0.01);InsRβ的磷酸化水平降低(P<0.05);IRS-1表达减少(P<0.05);PSD95表达减少(P<0.01)。结论新生IUGR大鼠脑内存在胰岛素信号通路障碍并发生了神经元可塑性的变化,这些变化可能增加成年后对神经变性病的易感性。

胰岛素样生长因子对IUGR胎盘功能影响的实验研究

目的通过L-精氨酸孕期干预后IUGR大鼠胎盘IGF-Ⅰ、IGF-Ⅱ及IGFBP-3水平的变化,探讨L-精氨酸的作用及其机制。方法被动吸烟法造IUGR大鼠模型,孕鼠随机分为4组:对照组、模型组、L-精氨酸小剂量和大剂量防治组。应用酶联免疫吸附法检测各组胎盘组织IGF-Ⅰ、IGF-Ⅱ及IGFBP-3含量。结果模型组大鼠胎盘重比对照组明显下降,L-精氨酸防治组与模型组相比,胎盘重量明显增加(P<0.01)。与对照组相比,模型组胎盘组织中IGF-Ⅰ、IGF-Ⅱ含量明显降低,IGFBP-3含量明显增高(P<0.01)。小剂量和大剂量L-精氨酸防治组与模型组相比,IGF-Ⅰ、IGF-Ⅱ含量明显增高,IGFBP-3含量明显降低(P<0.01)。结论L-精氨酸可增高宫内发育迟缓大鼠胎盘组织中IGF-Ⅰ、IGF-Ⅱ的含量,降低IGFBP-3含量,对胎鼠发育起保护作用。