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维生素B12活性形式的组合通过上调胎盘miR-16和miR-21水平改善了Wistar大鼠的胎儿生长。

Combination of vitamin B12 active forms improved fetal growth in Wistar rats through up-regulation of placental miR-16 and miR-21 levels.

作者信息

Shah Tejas, Mishra Sanjay, More Amol, Otiv Suhas, Apte Kishori, Joshi Kalpana

机构信息

Dr. Prabhakar Kore Basic Science Research Centre, KLE Academy of Higher Education and Research, KLE University, Nehru Nagar, Belagavi 590010, Karnataka, India.

APT Research Foundation, Sinhagad Road, Vadgaon Khurd, Pune 411041, Maharashtra, India.

出版信息

Life Sci. 2017 Dec 15;191:97-103. doi: 10.1016/j.lfs.2017.10.017. Epub 2017 Oct 12.

DOI:10.1016/j.lfs.2017.10.017
PMID:29032242
Abstract

AIM

Epidemiological studies have indicated importance of folate and vitamin (B12) during pregnancy. Also available evidence on efficacy of B12 forms viz. Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl) and Hydroxycobalamin (HCbl) in preventing or treating cobalamin deficiency is limited. The present study examines the effect of various forms of B12 in combination with folate during pregnancy and their effect on gestational outcomes.

MAIN METHOD

In the present study, we examined the effect of various vitamin B12 forms in presence of recommended folate (RFol: 400μg/day) and high folate (HFol: 5mg/day) on gestational outcomes in female Wistar rats.

FINDINGS

Dams dosed with excessive folate (HFol group) delivered low birth weight (LBW) offsprings (p<0.01) as compared to RFol dams. Plasma homocysteine levels were found to be significantly higher (p<0.05) in dams of HFol group and were reduced after vitamin B12 supplementation. Excessive folate supplementation and homocysteine levels showed inverse association with placental weight (p<0.01) and placental efficiency (p<0.05). B12 supplementation significantly up-regulated placental miR-16 and miR-21, associated with fetal growth which in turn reflected in improved birthweights. Supplementation with vitamin B12 forms, especially combination of active forms of cobalamins: MeCbl+AdCbl significantly increased birth weights (p<0.05) and modulated gestational outcomes in RFol as well as HFol supplemented dams.

SIGNIFICANCE

Our results indicated supplementing vitamin B12 along with folate during pregnancy had positive impact on the gestational outcomes. We have shown for the first time that combination of active forms of vitamin B12: MeCbl+AdCbl has better efficacy as compared to Cbl, MeCbl, AdCbl and HCbl alone.

摘要

目的

流行病学研究表明孕期叶酸和维生素B12很重要。关于维生素B12各形式即氰钴胺(Cbl)、甲钴胺(MeCbl)、腺苷钴胺(AdCbl)和羟钴胺(HCbl)在预防或治疗钴胺素缺乏症方面疗效的现有证据有限。本研究考察孕期各种形式的维生素B12与叶酸联合使用的效果及其对妊娠结局的影响。

主要方法

在本研究中,我们考察了在推荐叶酸量(RFol:400μg/天)和高叶酸量(HFol:5mg/天)存在的情况下,各种维生素B12形式对雌性Wistar大鼠妊娠结局的影响。

研究结果

与给予推荐叶酸量的母鼠相比,给予过量叶酸的母鼠(HFol组)所产仔鼠出生体重低(p<0.01)。发现HFol组母鼠血浆同型半胱氨酸水平显著更高(p<0.05),补充维生素B12后降低。过量补充叶酸和同型半胱氨酸水平与胎盘重量(p<0.01)和胎盘效率(p<0.05)呈负相关。补充维生素B12显著上调与胎儿生长相关的胎盘miR-16和miR-21,这反过来反映在出生体重的改善上。补充维生素B12各形式,尤其是钴胺素活性形式的组合:MeCbl+AdCbl显著增加出生体重(p<0.05),并调节了给予推荐叶酸量和高叶酸量补充剂的母鼠的妊娠结局。

意义

我们的结果表明孕期补充维生素B12和叶酸对妊娠结局有积极影响。我们首次表明,与单独使用Cbl、MeCbl、AdCbl和HCbl相比,维生素B12活性形式的组合:MeCbl+AdCbl具有更好的疗效。

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