Role of mammalian target of rapamycin signaling pathway in regulation of fatty acid oxidation in a preeclampsia-like mouse model treated with pravastatin / 中华医学杂志(英文版)

BACKGROUND@#Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several studies show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nω-nitro-L-arginine methyl ester (L-NAME) PE-like mouse model in our previous study. This study aimed to investigate the effect of mTOR signaling pathway in PE-like model treated with Pra.@*METHODS@#Pregnant mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from gestational 7th to 18th day. Giving Pra (L-NAME + Pra, Control + Pra, n = 8) or normal saline (NS; L-NAME + NS, Control + NS, n = 8) from gestational 8th to 18th day, the mice were sacrificed on day 18 and their liver and placental tissues were collected. Then the activation of mTOR and its substrates in the liver and placenta were detected. And the association between mTOR activation and serum free fatty acid (FFA) levels and the expression of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) were evaluated using Pearson correlation test. Differences between groups were analyzed using independent t-test or one-way analysis of variance (ANOVA).@*RESULTS@#Both in the maternal liver and placenta, the activation of mTOR protein and its effect on substrates increased significantly in the L-NAME + NS group and decreased significantly in the L-NAME + Pra group. The p-mTOR/mTOR protein ratio decreased in the L-NAME + Pra group significantly than that in the L-NAME + NS group both in liver and placenta (liver: 0.74 ± 0.08 vs. 0.85 ± 0.06, t = 2.95, P < 0.05; placenta: 0.63 ± 0.06 vs. 0.77 ± 0.06, t = 4.64, P < 0.05). The activation of mTOR protein in the liver and placenta negatively correlated with the expression of LCHAD in the L-NAME + NS group (liver: r = -0.745, P < 0.05; placenta: r = -0.833, P < 0.05) and that in the maternal liver negatively correlated with the expression of LCHAD (r = -0.733, P < 0.05) and positively with the serum FFA levels (r = 0.841, P < 0.05) in the L-NAME + Pra group.@*CONCLUSION@#The inhibition of mTOR signaling pathway might be involved in the regulation of FAO in mouse model treated with Pra.

Different Effects of Pravastatin on Preeclampsia-like Symptoms in Different Mouse Models / 中华医学杂志(英文版)

<p><b>Background</b>Pravastatin (Pra) exerts protective effects on preeclampsia. Preeclampsia is a multifactorial and pathogenic pathway syndrome. The present study compared the effects of Pra on clinical manifestations of preeclampsia in different pathogenic pathways.</p><p><b>Methods</b>Two different preeclampsia-like mouse models used in this study were generated with Nω-nitro-L-arginine methyl ester (L-NAME) and used lipopolysaccharide (LPS) from day 7 of gestation, respectively. Pra treatment was administered on day 2 after the models were established in each group (L-NAME + Pra, LPS + Pra, and Control + Pra, n = 8) or normal saline (NS) for the control group (L-NAME + NS, LPS + NS, and Control + NS, n = 8). Maternal weight, serum lipids, the histopathological changes, and lipid deposition in the liver and placenta were observed. The pregnancy outcomes were compared. The blood pressure analysis was carried out on repeated measurements of variance. Student's t-test was used for comparing the two groups. The enumeration data were compared by Chi-square test.</p><p><b>Results</b>The mean arterial pressure (MAP) and 24-h urinary protein in the L-NAME + NS and LPS + NS groups were significantly higher than the Control + NS group (F = 211.05 and 309.92 for MAP, t = 6.63 and 8.63 for 24-h urinary protein; all P < 0.05) and reduced in the L-NAME + Pra group as compared to the L-NAME + NS group (F = 208.60 for MAP, t = 6.77 for urinary protein; both P < 0.05). Urinary protein was decreased in the LPS + Pra group as compared to the LPS + NS group (t = 5.33; P < 0.05), whereas MAP had no statistical significance (F = 3.37; P > 0.05). Compared to the Control + NS group, the placental efficiency in the L-NAME + NS and LPS + NS groups decreased significantly (t = 3.09 and 2.89, respectively; both P < 0.05); however, no significant difference was observed in L-NAME + Pra and LPS + Pra groups (t = 1.37 and 0.58, respectively; both P > 0.05). Free fatty acid was elevated in the L-NAME + NS group as compared to the Control + NS group (t = 3.99; P < 0.05) at day 18 of pregnancy and decreased in the L-NAME + Pra group as compared to the L-NAME + NS group (t = 3.28; P < 0.05); however, no significant change was observed in the LPS model (F = 0.32; P > 0.05).</p><p><b>Conclusion</b>This study suggested that Pra affected the clinical manifestations differently in preeclampsia-like mouse models generated in various pathogenic pathways.</p>