Department of Obstetrics and Gynecology, Jingzhou Central Hospital, Jingzhou, City, 434020, Hubei Province, People's Republic of China.
J Assist Reprod Genet. 2021 Jul;38(7):1843-1851. doi: 10.1007/s10815-021-02158-5. Epub 2021 Mar 26.
To explore the role of silent information regulator 1 (SIRT1)-mediated Sonic Hedgehog (SHH) pathway in reduced uterine perfusion pressure (RUPP) model of preeclampsia (PE) in rats.
The pregnant rats were divided into sham, RUPP, RUPP + rSIRT1 (recombinant SIRT1 protein), RUPP + rSHH (recombinant SHH protein), and RUPP + rSIRT1+ Cy (cyclopamine, an SHH pathway inhibitor) groups, followed by the determination of mean arterial pressure (MAP) and pregnancy outcome. The gene or protein expression was determined by enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), or Western blotting.
RUPP rats showed increases MAP with the lower levels of vascular endothelial growth factor (VEGF) and nitrite and nitrate (NOx), as well as the higher levels of soluble FMS-like tyrosine kinase-1 (sFlt-1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in maternal plasma, which was attenuated after rSIRT1 or rSHH treatment. Besides, the improvement in the pregnancy outcome was seen in the rats from the RUPP + rSIRT1/rSHH groups as compared with the RUPP group. However, the therapeutic effect of rSIRT1 was reversed by cyclopamine. Placenta tissues of RUPP rats manifested the down-regulations of SIRT1, Patched-1 (PTCH1), and GLI family zinc finger 2 (GLI2), which were up-regulated in the RUPP + rSIRT1 group.
SIRT1 was down-regulated while SHH pathway was inhibited in the placental tissue of PE rats. SIRT1 improved the blood pressure, angiogenic imbalance, inflammation, and pregnancy outcome in PE rats via SHH pathway, supporting its potential use for the treatment of PE.
探讨沉默信息调节因子 1（SIRT1）介导的 Sonic Hedgehog（SHH）通路在大鼠子痫前期（PE）低子宫灌注压（RUPP）模型中的作用。
将妊娠大鼠分为假手术组、RUPP 组、RUPP+rSIRT1（重组 SIRT1 蛋白）组、RUPP+rSHH（重组 SHH 蛋白）组和 RUPP+rSIRT1+Cy（SHH 通路抑制剂环巴胺）组，然后测定平均动脉压（MAP）和妊娠结局。通过酶联免疫吸附试验（ELISA）、实时定量逆转录聚合酶链反应（qRT-PCR）或 Western blot 测定基因或蛋白表达。
RUPP 大鼠 MAP 升高，血管内皮生长因子（VEGF）和硝酸盐/亚硝酸盐（NOx）水平降低，母血浆可溶性 FMS 样酪氨酸激酶-1（sFlt-1）、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6水平升高，rSIRT1 或 rSHH 治疗后上述变化减轻。此外，与 RUPP 组相比，RUPP+rSIRT1/rSHH 组妊娠结局改善。然而，环巴胺逆转了 rSIRT1 的治疗效果。RUPP 大鼠胎盘组织中 SIRT1、 patched-1（PTCH1）和 Gli 家族锌指蛋白 2（GLI2）下调，而 RUPP+rSIRT1 组上调。
PE 大鼠胎盘组织中 SIRT1 下调，SHH 通路受抑制。SIRT1 通过 SHH 通路改善 PE 大鼠血压、血管生成失衡、炎症和妊娠结局，为其治疗 PE 提供了潜在的应用价值。
