孕期开始的持续维生素A缺乏加重LPS诱导的仔鼠肠上皮屏障功能障碍

发布时间：2018-02-15 08:04

本文关键词： 维生素A缺乏 RARβ 肠上皮屏障功能 LPS TLR ZO-　出处：《免疫学杂志》2017年10期 　论文类型：期刊论文

【摘要】：目的探讨孕期维生素A(VA)缺乏对LPS诱导的仔鼠肠上皮屏障功能障碍的影响。方法构建孕期开始的VA正常(VAN)和VA缺乏(VAD)母鼠模型,其子代(仔鼠)于6周龄时给予脂多糖(LPS)灌胃诱导肠道感染。高效液相色谱法(HPLC)检测血清视黄醇水平;ELISA试剂盒检测仔鼠血清二胺氧化酶(DAO)浓度;采用RT-PCR和Western blot技术测定RA受体(RARβ)、Toll样受体4和紧密连接蛋白ZO-2的变化。结果 VA营养水平与LPS处理均是血清视黄醇的影响因素(P0.000 1和P=0.035 9),但影响血清视黄醇水平的主要因素是VA营养水平(P0.000 1)。同时,VA水平与LPS处理也均是血清DAO水平的影响因素(P=0.048 1和P0.000 1),但LPS是引起DAO水平升高的主要因素(P0.000 1)。此外,VAD仔鼠结肠黏膜组织中的RARβ、TLR4和ZO-2的mRNA和蛋白表达水平均较VAN组显著降低。LPS处理后,RARβ的表达水平在VAN组进一步降低,VAD仔鼠结肠黏膜组织中TLR4和ZO-2的表达水平始终低于VAN组。结论孕期开始的持续的VA缺乏主要降低血清视黄酸水平及ZO-2的表达,LPS处理上调血清DAO水平及肠上皮细胞TLR4的表达,而RARβ的表达水平受到VAD及LPS的交互作用,提示VA缺乏可能会降低仔鼠肠道的天然免疫调节能力,降低肠道屏障功能,从而影响肠道的抗感染能力。
[Abstract]:Objective to investigate the effects of vitamin A (VA) deficiency during pregnancy on intestinal epithelial barrier dysfunction induced by LPS. At the age of 6 weeks, the offspring were given lipopolysaccharide (LPS) to induce intestinal infection. The serum retinol level was detected by HPLC and the serum diamine oxidase (DAO) concentration was detected by Elisa kit. RT-PCR and Western blot techniques were used to determine the changes of RAR 尾 -Toll-like receptor 4 and ZO-2. Results VA nutrition level and LPS treatment were the influencing factors of serum retinol, P0. 000 1 and P0. 039 9, but affected the serum retinol level. At the same time, the levels of VA and LPS were also the influencing factors of serum DAO level, but LPS was the main factor that caused the increase of DAO level. In addition, RAR 尾 TLR4 in colonic mucosa of rats with VAD was the main factor that caused the increase of DAO level. The expression level of mRNA and protein in VAN group was significantly lower than that in VAN group. The expression of TLR4 and ZO-2 in colonic mucosa of VAN group was significantly lower than that of VAN group. Conclusion the expression of TLR4 and ZO-2 in colonic mucosa of pregnant rats is lower than that of VAN group. The level of serum retinoic acid and the expression of ZO-2 were decreased by VA deficiency. LPS-induced upregulation of serum DAO level and the expression of TLR4 in intestinal epithelial cells were observed. However, the expression of RAR 尾 was affected by the interaction of VAD and LPS, suggesting that the deficiency of VA might decrease the innate immunomodulation ability and intestinal barrier function of neonatal rats, thus affecting the ability of intestinal anti-infection.
【作者单位】：重庆医科大学附属儿童医院营养研究室儿童发育疾病研究教育部重点实验室儿童发育重大疾病国家国际科技合作基地;
【基金】：国家自然科学基金(81070286,81470799) 重庆市渝中区科委项目(20120210)
【分类号】：R392

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