Title: Pravastatin alleviates TLR4 over-activation of placenta induced by lipopolysaccharide and promotes remodeling of uterine arterioles without impairing fetal development of rats

 

Authors: Muyi Yang1, Zhenyu Diao2, Zhiyin Wang1, Guijun Yan2, Guangfeng Zhao2, Mingming Zheng2, Anyi Dai2, Yimin Dai 2, Yali Hu1

 

Institutions: 1 Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China; 2Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.

 

Abstract: Preeclampsia (PE) is associated with an over-activation of innate immune system in placenta, in which toll-like receptor 4 (TLR4) plays an essential part. With its potent anti-inflammatory effects, statins have been suggested as potential prevention or treatment of PE, although the evidence remains inadequate. Herewith we investigated whether pravastatin could ameliorate PE-like phenotypes in a previously established LPS-induced rat model, through targetingTLR4/NF-kB pathway. The results showed that pravastatin reduced the blood pressure (maximum decline on GD12, 101. 33 2. 49mmHg vs. 118. 33 1. 37 mmHg, p < 0. 05) and urine protein level (maximum decline on GD9, 3726. 23 1572. 86 mg vs. 1991. 03 609. 37 mg, p < 0. 05), which were elevated following LPS administration. Pravastatin also significantly reduced the rate of fetal growth restriction in LPS-treated rats (34. 10% vs. 8. 99%, p < 0. 05). Further pathological analyses suggested a restoration of normal spiral artery remodeling in PE rats by pravastatin treatment. These effects of pravastatin were associated with decreased TLR4/NF-kB protein levels in placenta and IL-6/MCP-1 levels in serum. Additionally, no obvious abnormalities in fetal liver, brain, kidney were found after administration of pravastatin. These results provide supportive evidence of use of pravastatin in preventing PE.

 

Keywords: preeclampsia, pravastatin, toll-like receptor, fetal development

 

Full Text: JBR-2018-0039 pre-proof.pdf

 

J Biomed Res published on 05 June 2018, https://doi.org/10.7555/JBR.32.20180039