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培加巴林对鸡胚模型的视网膜致畸性。

Retinal teratogenicity of pregabalin in chick embryo model.

机构信息

Department of Pathology, School of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey.

出版信息

Cutan Ocul Toxicol. 2020 Dec;39(4):304-310. doi: 10.1080/15569527.2020.1802739. Epub 2020 Aug 11.

DOI:10.1080/15569527.2020.1802739
PMID:32722992
Abstract

BACKGROUND

Pregabalin is a gamma-aminobutyric acid analog that binds to the α2-δ subunits of the pre-synaptic voltage-dependent calcium channels of nerves with a high affinity and selectivity. In this study, the retinal teratogenic potential of pregabalin was investigated in a chick embryo model.

MATERIALS AND METHODS

Fertilised chicken eggs were divided into groups for administration with different doses of pregabalin. All eggs were opened on the 10th day of incubation. The embryos were dissected and the effects of pregabalin on the retina were investigated histopathologically, morphometrically, and immunohistochemically (Caspase-3).

RESULTS

There was no statistically significant difference between the low dose pregabalin, control, or vehicle control groups in terms of the number of retina layers and retinal thickness. Medium and high dose pregabalin caused a statistically significant decrease in the number of retina layers, as well as sensory retinal and pigment epithelium layer thicknesses. The outer nuclear and outer plexiform layer did not form in the group administered a medium dose. Similarly, the outer nuclear, outer plexiform, inner nuclear, and inner plexiform layer did not form in the high-dose group. No statistically significant difference was observed between the groups in terms of cellular damage and Caspase-3 expression.

CONCLUSION

The use of pregabalin during pregnancy compromises retinal development in a dose-dependent manner. The use of pregabalin in pregnancy causes the aforementioned defects in this system and it may have developmental effects that needs to be further evaluated.

摘要

背景

普瑞巴林是一种γ-氨基丁酸类似物,它以高亲和力和选择性与神经前突触电压依赖性钙通道的α2-δ亚基结合。在这项研究中,用鸡胚模型研究了普瑞巴林的视网膜致畸潜力。

材料和方法

将受精的鸡卵分为不同剂量普瑞巴林给药组。所有鸡蛋在孵化的第 10 天打开。胚胎被解剖,用组织病理学、形态计量学和免疫组织化学(半胱天冬酶-3)研究普瑞巴林对视网膜的影响。

结果

低剂量普瑞巴林、对照组和载体对照组之间,视网膜层数和视网膜厚度的数量没有统计学上的显著差异。中、高剂量普瑞巴林导致视网膜层数以及感觉视网膜和色素上皮层厚度的统计学显著减少。中剂量给药组的外核和外丛状层未形成。同样,高剂量组也未形成外核、外丛状层、内核和内丛状层。各组之间的细胞损伤和 Caspase-3 表达无统计学差异。

结论

妊娠期间使用普瑞巴林会导致视网膜发育受损,呈剂量依赖性。普瑞巴林在妊娠期间的使用会导致该系统出现上述缺陷,可能具有需要进一步评估的发育影响。

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