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The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia

  • Authors:
    • Zhao‑Heng Lin
    • Jing Jin
    • Xi‑Yun Shan

  • View Affiliations

  • Published online on: January 13, 2020     https://doi.org/10.3892/ijmm.2020.4465
  • Pages: 825-835

  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Preeclampsia (PE), a hypertensive disorder during pregnancy, has adverse effects to both the mother and the fetus. Maternal inflammatory and vascular endothelial dysfunction are important factors in the pathogenesis of PE. The present study aimed to investigate the effects of estradiol (E2) on inflammatory and endothelial dysfunction in an N (omega)‑nitro‑L‑arginine methyl ester (L‑NAME)‑induced rat model of PE. Adult pregnant female Sprague‑Dawley rats were divided into four equal groups between days 7 and 11 of gestation and treated as follows: i) Pregnant rats receiving daily intraperitoneal (i.p.) injections of equal volume of 0.9% normal saline (NS) (Control group, n=12); ii) pregnant rats receiving daily i.p. injections of L‑NAME at 50 mg/kg (L‑NAME group, n=12); iii) pregnant rats receiving a daily i.p. injection of 50 mg/kg L‑NAME and NS from day 11 (L‑NAME + NS group, n=12); and iv) pregnant rats receiving daily i.p. injections of 50 mg/kg L‑NAME and 100 µg/kg/day E2 from day 11 (L‑NAME + E2 group, n=12). On day 21, blood pressure (BP) and the level of 24‑h urine protein in the maternal rats, fetal weight and percentage of stillbirths following a cesarean section were recorded. The activities of nitric oxide (NO) and inducible NO synthase (iNOS), the levels of inflammatory cytokines [interleukin (IL)‑1β, IL‑6, interferon‑γ and monocyte chemoattractant protein‑1], adherence factors (CD49d, intracellular adhesion molecule 1 and lymphocyte function‑associated antigen‑1) and uterine angiogenic status (Fms‑like tyrosine kinase‑1, vascular cell adhesion molecule and matrix metalloproteinase 2/9) were also assessed. In addition, the histopathology of the placenta, the expression of estrogen receptor α 36 (ERα36), ERα, ERβ and G protein‑coupled ER, as well as the activation of the toll‑like receptor 4 (TLR4) signaling pathway (TLR4, myeloid differentiation primary response 88, IL‑1 receptor‑associated kinase 4 and tumor necrosis factor receptor‑associated factor 6) were evaluated by H&E staining, immunofluorescence and western blot assays. Treatment with L‑NAME increased the BP, urine protein and rate of stillbirths and suppressed fetal weight compared with those in the control group. The L‑NAME‑induced effects were attenuated by the administration of E2. In addition, the administration of E2 decreased inflammation and NO levels and altered the uterine angiogenic status. The histological analysis of PE rat placenta in the E2‑treated group confirmed the effects on biochemical parameters. Of note, E2 treatment significantly suppressed the TLR4 signaling pathway. In the rat model of PE, adverse outcomes including BP, fetal rat weight and proteinuria, high neonatal death rate, inflammatory response, oxidative stress and endothelial dysfunction were attenuated by exogenous E2 administration, which may present a novel approach for the clinical treatment of PE.
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March-2020
Volume 45 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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  • CiteScore Rank: Q1: #28/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 1.022
  • SCImago Journal Rank (SJR): 1.167
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Spandidos Publications style
Lin ZH, Jin J and Shan XY: The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia. Int J Mol Med 45: 825-835, 2020.
APA
Lin, Z., Jin, J., & Shan, X. (2020). The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia. International Journal of Molecular Medicine, 45, 825-835. https://doi.org/10.3892/ijmm.2020.4465
MLA
Lin, Z., Jin, J., Shan, X."The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia". International Journal of Molecular Medicine 45.3 (2020): 825-835.
Chicago
Lin, Z., Jin, J., Shan, X."The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia". International Journal of Molecular Medicine 45, no. 3 (2020): 825-835. https://doi.org/10.3892/ijmm.2020.4465