| Iron is a necessary trace element in the body,but iron deficiency generally affects animal production and human health.Oral ferric citrate can effectively prevent and improve iron deficiency anemia in patients with chronic kidney disease.However,long-term use can lead to iron overload and damage to jejunal mucosa.The long-term effect of ferric citrate on the jejunal mucosal barrier has not been systematically the study.Sixty nine-month-old C57BL/6 mice were randomly divided into four groups: low-dose group(FC,1.25%),middle-dose group(FC,2.5%),high-dose group(FC,5%).The control group was given the same amount of 0.9% saline.After 16 weeks,the level of iron in serum,liver,spleen,kidney,heart and jejunum was measured;the jejunum morphology was observed by HE staining;detection of goblet cells by AB-PAS staining;the level of D-LA in serum,SIg A and 8-OHd G in intestinal mucosa was measured by ELISA;the m RNA expressions of mucin 2,TFF3,tight junction protein,pro-inflammatory factor,chemokine and anti-inflammatory factor in jejunum was measured by q RT-PCR;the activity of oxidative damage and antioxidant capacity in jejunum was measured using Biochemical kit;the protein levels of proinflammatory factor,anti-inflammatory factor and occludin was measured by western blotting;1.The iron content in serum,liver,spleen,kidney,heart and jejunum of the mice in each group was significantly increased with the iron content(P<0.05),indicating that the iron overload model was successfully constructed.2.The HE staining showed that there was no any pathological changes in jejunum of mice.The PAS staining showed that middle-dose group and high-dose group significantly increased the number of goblet cells and intraepithelial lymphocytes in the jejunum.3.Compared with the control group,MDA and protein carbonyl in the jejunum were significantly or significantly increased(P<0.05 or P<0.01),and were dose-dependent.The content of 8-OHd G in the mice with iron overload was not significantly different from that in the control group.With the increase of iron supplementation dose,the GSH content and SOD activity in the jejunum of the mice with iron overload were significantly or significantly decreased(P<0.05 or P<0.01).GSH-Px,CAT activity and T-AOC were also lower than the control group with increasing dose,and the middle dose group and high dose group were significantly lower than the control group(P<0.01).The expression level of Nrf2 m RNA increased significantly with the increase of iron dose(P<0.05).4.The m RNA expression levels of TNF-?,IL-1?,IL-2,IL-6 and IL-8 in the iron overload group increased gradually with the increase of iron content in the stomach,and were significantly higher than the control group(P< 0.01);The expression of IFN-? m RNA was significantly increased in high dose group(P<0.05).Excess iron could decrease the m RNA expression levels of IL-4 and IL-10 in jejunum,medium and high doses of IL-4 and IL-10 m RNA.The control group showed a significant or extremely significant decrease(P < 0.05 or P < 0.01).The SIg A of jejunum mucosa was significantly increased in the middle dose and high dose groups(P<0.01).5.According to the index of jejunum mucosal barrier function in each group,the iron overload group reduced the expression of ZO-1,occludin,claudin-1,muc-2 and TFF3 in the colon(P<0.05)and increased the D-lactate content in serum(P<0.05).In a word,the ferric citrate solution can cause iron overload in the body.Iron overload reduce the antioxidant capacity of jejunal mucosa,cause oxidative stress,lead to lipids and proteins in jejunal mucosa.Oxidative damage of the jejunal mucosa can cause a decrease in the height of the long villi and the velvet ratio,affecting the morphological structure of the jejunum.Long-term administration of ferric citrate can increase the content of pro-inflammatory factors,inhibit the secretion of anti-inflammatory factors,and reduce the number of intestinal intraepithelial lymphocytes and SIg A content,resulting in impaired intestinal mucosal immune barrier.Long-term intragastric administration of iron citrate reduced the number of goblet cells,down-regulated the expression levels of MUC2,TFF3,ZO-1,occludin and claudin-1,and decreased the content of occludin protein,resulting in the destruction of intestinal epithelial tight junction and increased intestinal permeability,thereby damaging the mechanical barrier of jejunal mucosa.In conclusion,long-term administration of ferric citrate causes iron overload in the jejunum,causing oxidative damage to the jejunal mucosa,resulting in damage to the jejunal mucosal immune barrier and mechanical barrier. |
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