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胆钙化醇对实验性1型糖尿病中维生素D内分泌/旁分泌/自分泌系统关键成分的影响

Effects of Cholecalciferol on Key Components of Vitamin D-Endo/Para/Autocrine System in Experimental Type 1 Diabetes.

作者信息

Mazanova Anna, Shymanskyi Ihor, Lisakovska Olha, Hajiyeva Lala, Komisarenko Yulia, Veliky Mykola

机构信息

Department of Biochemistry of Vitamins and Coenzymes, Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine.

Department of Endocrinology, Bogomolets National Medical University, Kyiv, Ukraine.

出版信息

Int J Endocrinol. 2018 Feb 6;2018:2494016. doi: 10.1155/2018/2494016. eCollection 2018.

DOI:10.1155/2018/2494016
PMID:29552033
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5818969/
Abstract

OBJECTIVES

Recent prospective studies have found the associations between type 1 diabetes (T1D) and vitamin D deficiency. We investigated the role of vitamin D in the regulation of 25OHD-1-hydroxylase (CYP27B1) and VDR expression in different tissues of T1D rats.

DESIGN

T1D was induced in male Wistar rats by streptozotocin (55 mg/k b.w.). After 2 weeks of T1D, the animals were treated orally with or without vitamin D (cholecalciferol; 100 IU/rat, 30 days).

METHODS

Serum 25-hydroxyvitamin D (25OHD) was detected by ELISA. CYP27A1, CYP2R1, CYP27B1, and VDR were assayed by RT-qPCR and Western blotting or visualized by immunofluorescence staining.

RESULTS

We demonstrated that T1D led to a decrease in blood 25OHD, which is probably due to the established downregulation of CYP27A1 and CYP2R1 expression. Vitamin D deficiency was accompanied by elevated synthesis of renal CYP27B1 and VDR. Conversely, CYP27B1 and VDR expression decreased in the liver, bone tissue, and bone marrow. Cholecalciferol administration countered the impairments of the vitamin D-endo/para/autocrine system in the kidneys and extrarenal tissues of diabetic rats.

CONCLUSIONS

T1D-induced vitamin D deficiency is associated with impairments of renal and extrarenal CYP27B1 and VDR expression. Cholecalciferol can be effective in the amelioration of diabetes-associated abnormalities in the vitamin D-endo/para/autocrine system.

摘要

目的

近期的前瞻性研究发现了1型糖尿病（T1D）与维生素D缺乏之间的关联。我们研究了维生素D在调节T1D大鼠不同组织中25OHD-1-羟化酶（CYP27B1）和维生素D受体（VDR）表达中的作用。

设计

通过链脲佐菌素（55mg/kg体重）诱导雄性Wistar大鼠患T1D。T1D发病2周后，对动物进行口服维生素D（胆钙化醇；100IU/只大鼠，持续30天）或不进行维生素D处理。

方法

采用酶联免疫吸附测定法（ELISA）检测血清25-羟维生素D（25OHD）。通过逆转录定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹法检测CYP27A1、CYP2R1、CYP27B1和VDR，或通过免疫荧光染色进行可视化检测。

结果

我们证明T1D导致血液中25OHD水平降低，这可能是由于CYP27A1和CYP2R1表达下调所致。维生素D缺乏伴随着肾脏中CYP27B1和VDR合成增加。相反，肝脏、骨组织和骨髓中CYP27B1和VDR表达降低。给予胆钙化醇可对抗糖尿病大鼠肾脏和肾外组织中维生素D内分泌/旁分泌/自分泌系统的损伤。

结论

T1D诱导的维生素D缺乏与肾脏和肾外CYP27B1及VDR表达受损有关。胆钙化醇可有效改善糖尿病相关的维生素D内分泌/旁分泌/自分泌系统异常。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/11781db0f729/IJE2018-2494016.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/e30dce6dfba9/IJE2018-2494016.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/d69abc221aa0/IJE2018-2494016.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/4d314f1b4152/IJE2018-2494016.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/39c6eace72a6/IJE2018-2494016.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/11781db0f729/IJE2018-2494016.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/e30dce6dfba9/IJE2018-2494016.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/d69abc221aa0/IJE2018-2494016.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/4d314f1b4152/IJE2018-2494016.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/39c6eace72a6/IJE2018-2494016.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f7/5818969/11781db0f729/IJE2018-2494016.005.jpg

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