Abstract

Objectives

Fingolimod (FIN) is used for multiple sclerosis treatment and has potential antiapoptotic and anti-inflammatory effects. We aimed at expanding our knowledge on various immunohistochemical markers for elucidating the possible mechanisms of action of fingolimod in the placenta and fetal lung and brain.

Methods

Sixteen pregnant rats were divided into four groups. On gestational day 17, lipopolysaccharide (LPS) was injected intraperitoneally to induce preterm fetal injury followed by intraperitoneal injection of fingolimod. Hysterotomy for preterm delivery was performed 6 h after fingolimod was injected. The study groups included (1) control, (2) LPS (1 mg/kg), (3) FIN (4 mg/kg), and (4) FIN + LPS. Fetal brain and lung and placenta samples were collected for histopathological examination. Moreover, fetal lungs (surfactant protein-A (SP-A), SP-B, SP-D, caspase-3, and caspase-8), fetal brains (interleukin-10, interleukin-1β, TNF-α, caspase-8, glial fibrillary acidic protein, vimentin, myelin basic protein, and receptor activator of nuclear factor kappa), and placenta tissues (interleukin-10, interleukin-1β, TNF-α, caspase-3, and caspase-8) were immunohistochemically evaluated.

Results

Maternal fingolimod treatment led to attenuation of LPS-induced fetal brain, lung, and placental injury, as indicated by lower immunoexpression of inflammatory markers compared to LPS group (p < .0001 for all comparisons).

Conclusion

The findings of the present study confirm the neuroprotective effects of antenatally administered fingolimod, which also significantly improved preterm fetal lung injury and placental inflammation in LPS-exposed preterm pregnancies by possible antiapoptotic and anti-inflammatory effects.

中文翻译：

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绒毛膜羊膜炎诱发早产大鼠模型中母体芬戈莫德对胎盘及胎儿肺和脑的保护作用的免疫组织化学分析。

摘要

目标

芬戈莫德（FIN）用于多发性硬化症治疗，具有潜在的抗凋亡和抗炎作用。我们旨在扩大我们对各种免疫组化标记物的了解，以阐明芬戈莫德在胎盘以及胎儿肺和脑中可能的作用机制。

方法

将十六只怀孕的大鼠分为四组。在妊娠第17天，腹膜内注射脂多糖（LPS）诱发早产胎儿损伤，然后腹膜内注射芬戈莫德。注射芬戈莫德后6 h行子宫切开术以早产。研究组包括（1）对照，（2）LPS（1 mg / kg），（3）FIN（4 mg / kg）和（4）FIN + LPS。收集胎儿脑，肺和胎盘样本以进行组织病理学检查。此外，胎儿的肺脏（表面活性蛋白A（SP-A），SP-B，SP-D，caspase-3和caspase-8），胎儿的大脑（白介素10，白介素-1β，TNF-α，caspase- 8，神经胶质纤维酸性蛋白，波形蛋白，髓磷脂碱性蛋白和核因子κ的受体激活剂，以及胎盘组织（白介素10，白介素1β，TNF-α，胱天蛋白酶3，

结果

母体芬戈莫德治疗导致LPS诱导的胎儿脑，肺和胎盘损伤的减轻，炎症标志物的免疫表达低于LPS组，这表明炎症标志物的免疫表达较低（所有比较，p <.0001）。

结论

本研究的结果证实了产前服用芬戈莫德的神经保护作用，它通过可能的抗凋亡和抗炎作用，还显着改善了LPS暴露的早产儿的早产儿肺损伤和胎盘炎症。