Effect of edaravone on pregnant mice and their developing fetuses subjected to placental ischemia.

Effect of edaravone on pregnant mice and their developing fetuses subjected to placental ischemia.
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DOI:
10.1186/s12958-021-00707-2
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发表时间:
2021-02-06
期刊:
Reproductive biology and endocrinology : RB&E
影响因子:
--
通讯作者:
Abe K
Abe K
中科院分区:
其他
文献类型:
--
作者:
Atallah M;Yamashita T;Abe K

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越来越多的证据表明,子宫灌注压降低(RUPP)触发了导致先兆子痫的级联事件。依达拉奉是一种强大的自由基清除剂,由于其抗氧化应激和抗炎特性,用于治疗缺血/再灌注疾病。在此,我们研究了依达拉奉(3 mg/kg)对RUPP诱导的胎盘缺血小鼠模型的不同母体和胎儿结局的影响。在妊娠第13天(GD)进行RUPP手术,然后从GD 14至GD 18(处死日)注射依达拉奉。结果显示,依达拉奉注射液能显著降低母血血压(113.2 ± 2.3 mmHg),而RUPP组血压为131.5 ± 1.9 mmHg。与RUPP组(54.4%)相比,依达拉奉可增加胎儿存活率(75.4%),与RUPP组相比,可增加胎儿长度、体重和胎儿-胎盘比(RUPP组和RUPP-依达拉奉组分别为7.2和5.7)。此外,RUPP导致许多胎儿形态异常以及严重的骨化延迟,然而依达拉奉减少了形态异常并增加了胎儿内骨骼的骨化。依达拉奉改善了母体肾脏和心脏的组织病理学结构,并降低了升高的血尿素和肌酐水平(31.5 ± 0.15 mg/dl(RUPP),25.6 ± 0.1 mg/dl尿素(RUPP+依达拉奉)和5.4 ± 0.1 mg/dl(RUPP),3.5 ± 0.1 mg/dl(RUPP+依达拉奉),肌酐),并降低母体肾脏中的裂解半胱天冬酶-3表达。总之,本研究表明,我们的RUPP小鼠模型重现了先兆子痫症状,依达拉奉注射液改善了大多数这些异常,表明其在先兆子痫治疗方案中的有效性和潜在应用。在线版本包含补充材料,可通过10.1186/s12958-021-00707-2获得。
Growing evidence indicates that reduced uterine perfusion pressure (RUPP) triggers the cascade of events leading to preeclampsia. Edaravone is a powerful free radical scavenger used for the treatment of ischemia/reperfusion diseases due to its anti-oxidative stress and anti-inflammatory properties. Here we investigate the effect of edaravone (3 mg/kg) on different maternal and fetal outcomes of RUPP-induced placental ischemia mice model. RUPP surgery was performed on gestation day (GD) 13 followed by edaravone injection from GD14 to GD18, sacrifice day. The results showed that edaravone injection significantly decreased the maternal blood pressure (113.2 ± 2.3 mmHg) compared with RUPP group (131.5 ± 1.9 mmHg). Edaravone increased fetal survival rate (75.4%) compared with RUPP group (54.4%), increased fetal length, weights, and feto-placental ratio (7.2 and 5.7 for RUPP and RUPP-Edaravone groups, respectively) compared with RUPP group. In addition, RUPP resulted in many fetal morphological abnormalities as well as severe delayed ossification, however edaravone decreased the morphological abnormalities and increased the ossification of the fetal endoskeleton. Edaravone improved the histopathological structure of the maternal kidney and heart as well as decreased the elevated blood urea and creatinine levels (31.5 ± 0.15 mg/dl (RUPP), 25.6 ± 0.1 mg/dl (RUPP+edaravone) for urea and 5.4 ± 0.1 mg/dl (RUPP), 3.5 ± 0.1 mg/dl (RUPP+edaravone) for creatinine) and decreased cleaved caspase-3 expression in the maternal kidney. In conclusion, this study demonstrated that our RUPP mice model recapitulated preeclampsia symptoms and edaravone injection ameliorated most of these abnormalities suggesting its effectiveness and potential application in preeclampsia treatment regimes. The online version contains supplementary material available at 10.1186/s12958-021-00707-2.
小鼠先兆子痫的子宫灌注压力(RUPP)模型降低。
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