孕马孕期地塞米松治疗对产后马驹胰腺β细胞功能的影响。

Valenzuela O A, Jellyman J K, Allen V L, Holdstock N B, Fowden A L

Department of Physiology, Development and Neuroscience, University of Cambridge, CB2 3EG, UK.

Department of Clinical Veterinary Medicine, University of Cambridge, CB2 3EG, UK.

Equine Vet J. 2017 Jan;49(1):99-106. doi: 10.1111/evj.12560. Epub 2016 Feb 15.

REASONS FOR PERFORMING STUDY

Synthetic glucocorticoids are used to treat inflammatory conditions in horses. In other pregnant animals, glucocorticoids are given to stimulate fetal maturation with long-term metabolic consequences for the offspring if given preterm. However, their metabolic effects during equine pregnancy remain unknown.

OBJECTIVE

Thus, this study investigated the metabolic effects of dexamethasone administration on pregnant pony mares and their foals after birth.

STUDY DESIGN

Experimental study.

METHODS

A total of 3 doses of dexamethasone (200 μg/kg bwt i.m.) were given to 6 pony mares at 48 h intervals beginning at ≈270 days of pregnancy. Control saline injections were given to 5 mares using the same protocol. After fasting overnight, pancreatic β cell responses to exogenous glucose were measured in the mares before, during and after treatment. After birth, pancreatic β cell responses to exogenous glucose and arginine were measured in the foals at 2 and 12 weeks.

RESULTS

In mares during treatment, dexamethasone but not saline increased basal insulin concentrations and prolonged the insulin response to exogenous glucose. Basal insulin and glucose concentrations still differed significantly between the 2 groups 72 h post treatment. Dexamethasone treatment significantly reduced placental area but had little effect on foal biometry at birth or subsequently. Foal β cell function at 2 weeks was unaffected by maternal treatment. However, by 12 weeks, pancreatic β cell sensitivity to arginine, but not glucose, was less in foals delivered by dexamethasone- than saline-treated mares.

CONCLUSIONS

Dexamethasone administration induced changes in maternal insulin-glucose dynamics, indicative of insulin resistance and had subtle longer term effects on post natal β cell function of the foals. The programming effects of dexamethasone in horses may be mediated partially by altered maternal metabolism and placental growth.

开展本研究的原因

合成糖皮质激素用于治疗马的炎症性疾病。在其他怀孕动物中，给予糖皮质激素可刺激胎儿成熟，但如果早产给药，会对后代产生长期的代谢影响。然而，它们在马妊娠期间的代谢作用尚不清楚。

目的

因此，本研究调查了地塞米松给药对怀孕母马及其出生后驹的代谢影响。

研究设计

实验研究。

方法

从妊娠约270天开始，每隔48小时给6匹母马肌肉注射共3剂地塞米松（200μg/kg体重）。按照相同方案给5匹母马注射对照生理盐水。过夜禁食后，在治疗前、治疗期间和治疗后测量母马胰腺β细胞对外源葡萄糖的反应。出生后，在2周和12周时测量驹胰腺β细胞对外源葡萄糖和精氨酸的反应。

结果

在治疗期间的母马中，地塞米松而非生理盐水增加了基础胰岛素浓度，并延长了对外源葡萄糖的胰岛素反应。治疗后72小时，两组之间的基础胰岛素和葡萄糖浓度仍有显著差异。地塞米松治疗显著减小了胎盘面积，但对出生时或随后驹的生物测量影响不大。2周时驹的β细胞功能不受母体治疗的影响。然而，到12周时，地塞米松处理的母马所生驹的胰腺β细胞对精氨酸（而非葡萄糖）的敏感性低于生理盐水处理的母马所生驹。