Department of Obstetrics and Gynecology, Jinan Maternity and Childcare Hospital, Jinan, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6591-6598. doi: 10.26355/eurrev_201810_16133.
Pathogenesis factor of pregnant hypertension is still unclear and lacks of effective treatment. MiR-155 is a recently discovered miRNA molecule with differential expression in pregnant hypertension, which participates in the disease regulation. As a downstream target gene of miR-155, FOXO3a is correlated with blood pressure regulation. We investigated the regulatory role and mechanism of miR-155 in pregnant hypertension.
We established a pregnant hypertension rat model, on which miR-155 inhibitor or FOXO3a siRNA was applied, followed by HE staining, 24 h urea protein, blood pressure and serum creatine assay to evaluate disease severity.
MiR-155 expression was significantly elevated in model rats, accompanied by a reduction of the FOXO3a level. MiR-155 inhibitor suppressed miR-155 expression, increased FOXO3a level and placental tissue morphology by HE staining, and depressed blood pressure as well as serum creatine level. Downregulation of FOXO3a by specific siRNA resulted in opposite effects. These results illustrated the miR-155 mediated FOXO3a expression in pregnant hypertension.
The inhibition of miR-155 improves the damage of pregnant hypertension via the upregulation of FOXO3a, which provides academic leads for the future therapy of pregnant hypertension.
妊娠高血压的发病机制尚不清楚,缺乏有效治疗方法。miR-155 是一种最近发现的 miRNA 分子,在妊娠高血压中表达差异,参与疾病调节。作为 miR-155 的下游靶基因,FOXO3a 与血压调节有关。我们研究了 miR-155 在妊娠高血压中的调节作用及其机制。
我们建立了妊娠高血压大鼠模型,应用 miR-155 抑制剂或 FOXO3a siRNA,然后进行 HE 染色、24 小时尿素蛋白、血压和血清肌酐测定,以评估疾病严重程度。
模型大鼠中 miR-155 表达明显升高,同时 FOXO3a 水平降低。miR-155 抑制剂抑制 miR-155 表达,通过 HE 染色增加 FOXO3a 水平和胎盘组织形态,降低血压和血清肌酐水平。特异性 siRNA 下调 FOXO3a 则产生相反的效果。这些结果表明 miR-155 通过调节 FOXO3a 在妊娠高血压中的表达。
miR-155 的抑制通过上调 FOXO3a 改善妊娠高血压的损伤,为妊娠高血压的未来治疗提供了学术依据。