摘要
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-κB 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） μg vs.（1,991.03 ±609.37）μg,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-κB 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.
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-κB 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） μg vs.（1,991.03 ±609.37）μg,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-κB 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.
基金
funded by the following Grants:National Natural Science Foundation of China,Grant/Award Number:81370724,81571463 and 81401225
Innovative Research Program for Postgraduate in Higher Education Institutions of Jiangsu Province for the year 2016,Grant/Award Number:KYLX16_1111
