Sustainable vitamin A deficiency from the beginning of gestation aggravates intestinal barrier dysfunction in the offspring with LPS treatment

XIAO Lu; CUI Ting; LI Yingying; GAO Yuan; LI Tingyu; CHEN Jie

doi:10.13431/j.cnki.immunol.j.20170147

Abstract：To investigate the effect of vitamin A deficiency from the beginning of gestation on intestinal epithelial barrier function in the offspring with LPS treatment,pregnant rat models of vitamin A normal (VAN) and vitamin A deficiency (VAD) were constructed and the lipopolysaccharide (LPS) was intragastrically administrated to the pups at 6-week old for inducing their intestinal infection.The levels of serum retinol were detected by high performance liquid chromatography (HPLC),and the intestinal epithelial permeability was tested by using the ELISA kit of rat serum diamine oxidase (DAO).The levels of RARβ,TLR4 and ZO-2 mRNA and protein expression in the mucosal layer of colon tissues were analyzed by real-time PCR and Western blotting.The status of VA nutrition was the main influence factor to the serum retinol level (P＜0.000 1),though both the VA nutritional level and LPS treatment were the effect factors to the levels of serum retinol level (P＜0.000 1,P=0.035 9).Meanwhile,the bonferroni post-tests found that the LPS challenge was the major factor leading to increase of serum DAO levels (P＜0.000 1),though both the serum retinol level and LPS treatment were the effect factors to the levels of DAO (P=0.048 1,P＜0.000 1).Furthermore,The PCR and Western blot results showed that both mRNA and protein levels of RARβ,TLR4 and ZO-2 in the mucosal layer of VAD colon tissues were significantly decreased compared with those of VAN pups.The LPS infection significantly down-regulated the level of RARβ mRNA expression in the VAN group,while also statistically decreased the levels of TLR4 and ZO-2 expressions in the VAD colon tissues compared to those of the VAN group.Taken together,sustainable vitamin A deficiency from the beginning of gestation markably reduces the levels of serum retinal and the expression of ZO-2 in intestinal epithelial cells,while LPS treatment up-regulates the serum DAO concentration and TLR4 expression in the intestinal epithelium.However,the level of RARβ expression is affected by interaction between VAD and LPS treatments.These results suggest that VAD maybe decrease the innate immune regulation ability of pups' intestine,and weaken intestinal barrier function,thus affecting the anti-infection capability of intestine in the pups.