Effect Of Curcumin On Intestinal Morphology And Function Of Weaned Piglets With Intrauterine Growth Retardation

Intrauterine growth retardation(IUGR)refers to the impaired growth and development of a mammalian embryo or fetus,which is manifested by a fetus whose growth rate is lower than that of a normal fetus.IUGR has been a major concern for global human health and animal production.About 5%to 7%of infants are IUGR,and 10%to 20%of newborn piglets are IUGR in the world.The intestine is an important place for animal nutrition digestion and metabolism,and it is also the largest immune organ.It has important significance for animal growth and immune defense.Curcumin is a natural antioxidant that extracted from turmeric and has physiological functions such as anti-oxidation,anti-inflammatory,anti-tumor,hypolipidemic and immune function enhancement.Since curcumin has not been studied in IUGR weaned piglets,this study used IUGR weaned piglets as an animal model to investigate the effects of curcumin on the intestinal morphology and function of IUGR weaned piglets,and to provide new strategies for improving intestinal function damage in IUGR offspring.The study is divided into the following three parts:1.Effect of curcumin on growth,intestinal tissue morphology and and nutrient digestion of weaned piglets with intrauterine growth retardation16 newborn normal birth weight(NBW)and IUGR for each newborn piglet were selected,half male and female.The piglets weaned on the 26 d,fed basal diet or curcumin diet(basic diet+400 mg/kg curcumin),N(NBW+basic diet),NC(NBW+curcumin diet),I(IUGR+basis diet)and IC(IUGR+curcumin diet),8 in each group.The piglets were slaughtered at 50 d.Results:(1)Compared with group N,IUGR significantly reduced weight gain(WG)and feed intake(FI)(P<0.05).Compared with group I,curcumin significantly increased WG and FI(P<0.05).(2)Compared with group N,IUGR significantly reduced the absolute length of the duodenum(P<0.05),the relative length of the duodenum and the jejunum(P<0.05).Compared with group I,curcumin significantly increased the absolute length of duodenum and jejunum(P<0.05),and significantly increased the relative length of duodenum(P<0.05).(3)Compared with group N,IUGR significantly reduced duodenal villus height(VH),villus width(VW)and villus height/crypt depth(VCR),VH and VCR in the jejunum,VH,VW and VCR in the ileum(P<0.05),and significantly increased crypt depth(CD)in duodenum,jejunum and ileum(P<0.05).Compared with group Ⅰ,curcumin significantly increased duodenal VH and VCR,jejunal VH and VCR,and ileal VH,VW and VCR(P<0.05),and significantly reduced CD in duodenum,jejunum and ileum of group ⅠC(P<0,05).(4)Compared with group N,the small intestine intestine villi of the IUGR weaned piglets were easily damaged,broken,shorter and different in length.Compared with group Ⅰ,curcumin significantly improved the length and integrity of intestinal villi,and the number of villus fractures decreased.Compared with group I,curcumin significantly increased the length of the intestinal microvilli,and the jejunum was more pronounced.(5)Compared with group N,IUGR significantly reduced the apparent digestibility of organic matter(OM)in weaned piglets(P<0.05).Compared with group Ⅰ,curcumin significantly increased the apparent digestibility of DM,CP and EE(P<0.05).(6)Compared with group N,IUGR significantly reduced the activities of maltase and lactase in jejunum,maltase and sucrase in ileum(P<0.05).Compared with group Ⅰ,curcumin significantly enhanced the activity of lactase in ileum(P<0.05).(7)Compared with group N,IUGR significantly decreased serum insulin-like growth factor(IGF-1)and IGF-Ⅰ levels in jejunum,and the mRNA expression of IGF-Ⅰ in the jejunum and ileum(P<0.05).Compared with group Ⅰ,curcumin significantly increased the content of IGF-Ⅰ and the expression of IGF-Ⅰ mRNA in ileum(P<0.05).In conclusion,curcumin can also increase intestinal disaccharidase activity,insulin-like growth factor(IGF-Ⅰ)content and IGF-Ⅰ mRNA expression in ileum,and increased intestinal villi,microvilli length.Therefore,curcumin can improve the intestinal digestion and absorption function of IUGR weaned piglets and promote growth and development.2.Effect of curcumin on intestinal antioxidant function in weaned piglets with intrauterine growth retardationThe experiment was designed same with the experiment 1.Results:(1)Compared with group N,IUGR significantly increased malondialdehyde(MDA)in the jejunum of weaned pigs(P<0.05).Curcumin significantly decreased the content of protein carbonyl(PC)in jejunum and ileum,8-hydroxyl-2’-deoxyguanosine(8-OHDG)in jejunum and MDA in ileum compared with group Ⅰ(P<0.05).(2)Compared with group N,IUGR significantly reduced activity of total superoxide dismutase(T-SOD),glutathione peroxidase(GSH-Px)and glutathione(GSH)content in jejunum(P<0.05);after addition of curcumin,activities of the total antioxidant capacity(T-AOC),catalase(CAT)in group ⅠC.(3)Compared with group N,IUGR significantly decreased activity of T-SOD,CAT,GSH-Px and GSH content in ileum(P<0.05),and significantly increased hydrogen peroxide(H2O2)content(P<0.05).Compared with group Ⅰ,curcumin significantly increased activity of CAT,GSH-Px(P<0.05)and significantly decreased H2O2 content(P<0.05).(4)Compared with group N,IUGR significantly reduced mRNA expression of NF-E2-related factor 2(Nrf2),KEAP1,SOD,GSH-Px1,glutathione S-transferase(GST),NAD(P)H:quinone oxidoreductase 1(NQO1),GCLM,HO-1,thioredoxin reductase 1(TXNRD1)(P<0.05).Compared with group Ⅰ,curcumin significantly increased the mRNA expression of Nrf2,CAT,SOD,GST,NQOl and TXNRD1 in jejunum(P<0.05).(5)Compared with group N,IUGR significantly reduced the mRNA expression of CAT in ileum(P<0.05).Compared with group Ⅰ,curcumin significantly increased the mRNA expression of Nrf2,GST,SOD,GSH-Px1,NQO1 and TXNRD1 in ileum(P<0.05).In conclusion,IUGR can cause oxidative stress in the intestinal tract of weaned piglets and destroy the antioxidant defense system.Curcumin has certain effect in alleviating intestinal oxidative stress and improving intestinal antioxidant function in IUGR-induced piglets.3.Effect of curcumin on intestinal immune function in weaned piglets with intrauterine growth retardationThe experiment was designed same with the experiment 1.Results:(1)Compared with group N,IUGR significantly increased the number of white blood cells(P<0.05)and significantly decreased the number of platelets(P<0.05).Compared with group Ⅰ,curcumin significantly decreased the number of red blood cells(P<0.05)and significantly increased the number of platelets(P<0.05).(2)Compared with group N,IUGR significantly increased the content of interleukin-1β(IL-1β),interleukin-2(IL-2),interleukin-6(IL-6),interleukin-10(IL-10),and tumor necrosis factor-a(TNF-α)content(P<0.05),significantly reduced the content of immunoglobulin A(IgA),immunoglobulin G(IgG)and immunoglobulin M(IgM)(P<0.05).Compared with group Ⅰ,curcumin significantly decreased the levels of IL-1β,IL-2,IL-4,IL-6 and TNF-α in blood(P<0.05),and significantly increased content of IL-10,IgG,IgM and secretory immunoglobulin A(sIgA)(P<0.05).(3)Compared with group N,IUGR significantly reduced the content of IL-10 in jejunum(P<0.05).Compared with group Ⅰ,curcumin significantly decreased the levels of IL-1β,IL-2 and TNF-α in jejunum(P<0.05),and significantly decreased content of IL-1β,IL-2,IL-4,IL-6 and TNF-α in ileum(P<0.05).(4)Compared with group N,IUGR significantly reduced the content of IgA,IgG and sIgA in jejunum(P<0.05).Compared with group I,curcumin significantly increased content of IgG(P<0.05)and significantly decreased content of IgM in jejunum(P<0.05);curcumin significantly increased levels of IgA,IgG,IgM and sIgA in ileum(P<0.05).(5)Compared with group N,IUGR significantly decreased the mRNA expression of IL-10,CD4 and CD8 in jejunum and ileum(P<0.05),and significantly increased the mRNA expression of IL-1β and TNF-α in ileum(P<0.05).Compared with group I,curcumin significantly decreased the mRNA expression of IL-1β,TNF-α and major histocompatibility complex Ⅱ(MHC-Ⅱ)in jejunum(P<0.05),and significantly increased mRNA expression of IL-10,CD4 and CD8 in jejunum(P<0.05);compared with group Ⅰ,curcumin significantly decreased the mRNA expression of IL-1β and MHC-Ⅱ in ileum(P<0.05),and significantly increased mRNA expression of IL-10,CD4 and CD8 in ileum(P<0.05).In conclusion,IUGR resulted in up-regulation of immune inflammatory responses in weaned piglets,cytokine secretion disorders,and decreased levels of serum IgA,IgG,IgM,and jejunal mucosa IgA,IgG,and sIgA.Curcumin can alleviate the adverse effects of IUGR on the immune function of weaned piglets.Based on the aforementioned results,it can be therefore concluded that:(1)IUGR not only significantly reduced the growth performance of weaned piglets,but also damaged the morphological structure,digestion and absorption function,antioxidant function and immune function of intestinal mucosa.(2)Dietary supplementation of curcumin can increase intestinal disaccharidase activity,IGF-Ⅰ content and IGF-Ⅰ mRNA expression in ileum,increase intestinal villi and microvilli length,and improve intestinal digestion and absorption function of IUGR weaned piglets and promote growth and development.(3)Dietary supplementation of curcumin can significantly reduce the content of MDA,PC and 8-OHDG,increase the activitices of antioxidant enzymes and non-enzymatic antioxidants and related gene expression levels.(4)Dietary supplementation of curcumin can alleviate the adverse effects of IUGR on immune function of weaned piglets by reducing the levels and expression levels of pro-inflammatory factors such as IL-1β and increasing the content of IgA and other immunoglobulins.