边缘性维生素 A 缺乏症影响大鼠睑板腺中维 A 酸受体和维 A 酸 X 受体的表达水平和定位。

Marginal Vitamin A Deficiency Affects the Expression Levels and Localization of Retinoic Acid Receptor and Retinoid X Receptor in Rats Meibomian Gland.

机构信息

a Department of Ophthalmology , Children's Hospital, Chongqing Medical University , Chongqing , China.

b Children Nutrition Research Center , Children's Hospital of Chongqing Medical University , Chongqing , China.

出版信息

Curr Eye Res. 2019 Apr;44(4):368-375. doi: 10.1080/02713683.2018.1554154. Epub 2018 Dec 10.

DOI:10.1080/02713683.2018.1554154

PMID:30512978

Abstract

PURPOSE

To assess the effects of marginal vitamin A deficiency (MVAD) on rat Meibomian gland morphology as well as retinoic acid receptor (RAR) and retinoid X receptor (RXR) amounts and localization.

METHODS

Eight adult female rats were randomized into MVAD and vitamin A normal (VAN) groups, and fed vitamin A-deficient and normal control diets, respectively, for 3 weeks before mating. At postnatal week 4 (P4w), eight newborn animals in both groups were euthanized, respectively. Then, serum retinol levels were analyzed. Meibomian glands from P4w animals were further assessed upon hematoxylin and eosin staining. RAR and RXR gene and protein expression amounts were detected by real time polymerase chain reaction (qRT-PCR), immunofluorescence and western blotting, respectively.

RESULTS

Secretory cell nuclei had reduced areas, while the multilayered squamous epithelium of the ductule was overtly thinner in MVAD rats compared with VAN animals. RXR-α showed highest mRNA amounts among all RA receptors; compared with control values, RXR-α showed overtly decreased mRNA amounts in animals with MVAD. In addition, compared with normal rats, MVAD rats had starkly lower RXR-α and RXR-γ expression levels. Furthermore, only the RXR-α protein was detected in the nucleus of cells forming the multilayered squamous epithelium of the ductule in VAN rats.

CONCLUSION

RARs and RXRs may be involved in the regulation of Meibomian gland function. RXR-α and 9-cis RA signaling affects Meibomian gland function, and the mechanisms of retinoids on secretory cells and the ductule epithelium may differ.

ABBREVIATIONS

MVAD: marginal vitamin A deficiency; RAR: retinoic acid receptor; RXR: retinoid X receptor; VAN: vitamin A normal; RA: retinoic acid; RAREs: retinoic acid responsive elements; HPLC: high performance liquid chromatography; atRA: all-trans retinoic acid; MGD: Meibomian gland dysfunction; CRABPs: cellular retinoic acid-binding proteins.

摘要

目的

评估边缘性维生素 A 缺乏症 (MVAD) 对大鼠睑板腺形态以及维甲酸受体 (RAR) 和视黄醛 X 受体 (RXR) 数量和定位的影响。

方法

将 8 只成年雌性大鼠随机分为 MVAD 和维生素 A 正常 (VAN) 组，分别喂养维生素 A 缺乏和正常对照饮食 3 周后交配。在产后第 4 周 (P4w)，两组各有 8 只新生动物被安乐死。然后分析血清视黄醇水平。通过苏木精和伊红染色进一步评估 P4w 动物的睑板腺。通过实时聚合酶链反应 (qRT-PCR)、免疫荧光和 Western 印迹分别检测 RAR 和 RXR 基因和蛋白表达量。

结果

与 VAN 动物相比，MVAD 大鼠的分泌细胞核面积减小，而小管的多层鳞状上皮明显变薄。在所有 RA 受体中，RXR-α 显示出最高的 mRNA 含量；与对照值相比，MVAD 动物的 RXR-α mRNA 含量明显降低。此外，与正常大鼠相比，MVAD 大鼠的 RXR-α 和 RXR-γ 表达水平明显降低。此外，在 VAN 大鼠形成小管多层鳞状上皮的细胞核中仅检测到 RXR-α 蛋白。