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Muyi Yang,Zhenyu Diao,Zhiyin Wang,Guijun Yan,Guangfeng Zhao,Mingming Zheng,Anyi Dai,Yimin Dai,Yali Hu.Journal of Biomedical Research,2018,32(4):288-297
Pravastatin alleviates lipopolysaccharide-induced placental TLR4 over-activation and promotes uterine arteriole remodeling without impairing rat fetal development
Received:April 17, 2018  Revised:March 23, 2018
DOI10.7555/JBR.32.20180039
Keywordspreeclampsia, arteriole remodeling pravastatin, toll-like receptor 4, fetal development
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Muyi Yang Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu , China
Zhenyu Diao Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing,Jiangsu , China.
Zhiyin Wang Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu , China
Guijun Yan Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing,Jiangsu , China.
Guangfeng Zhao Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing,Jiangsu , China.
Mingming Zheng Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing,Jiangsu , China.
Anyi Dai Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing,Jiangsu , China.
Yimin Dai Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing,Jiangsu , China.
Yali Hu Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu , China
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Abstract
      Preeclampsia is associated with over-activation of the innate immune system in the placenta, in which toll-like receptor 4 (TLR4) plays an essential part. With their potent anti-inflammatory effects, statins have been suggested as potential prevention or treatment of preeclampsia, although evidence remains inadequate. Herewith, we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide (LPS)-induced rat preeclampsia model, through targeting the TLR4/NF-kB pathway. The results showed that pravastatin reduced the blood pressure [maximum decline on gestational day (GD) 12, (101.33 \ 2.49) mmHg vs. (118.3 \ 1.37) mmHg, P < 0.05] and urine protein level [maximum decline on GD9, (3,726.23 \ 1,572.86) mg vs. (1,991.03 \ 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 preeclampsia rats by pravastatin treatment. These effects of pravastatin were associated with decreased TLR4/NF-kB protein levels in the placenta and IL-6/MCP-1 levels in serum. Additionally, no obvious abnormalities in fetal liver, brain, and kidney were found after administration of pravastatin. These results provide supportive evidence for use of pravastatin in preventing preeclampsia.
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