Role of mammalian target of rapamycin signaling pathway in regulation of fatty acid oxidation in a preeclampsia-like mouse model treated with pravastatin  

作　　者：Jing Huai Zi Yang Yan-Hong Yi Guang-Jiao Wang 

机构地区：[1]Department of Obstetrics and Gynecology. Peking University Third Hospital, Beijing 100191, China

出　　处：《Chinese Medical Journal》2019年第6期671-679,共9页中华医学杂志（英文版）

基　　金：grants from the National Natural Science Foundation of China (No. 81370723);Beijing Municipal Natural Science Foundation (No. 7132215).

摘　　要：Background: Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nio-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 mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from 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 express

关 键 词：PREECLAMPSIA MTOR SIGNALING pathway PRAVASTATIN FATTY acid oxidation 

分 类 号：R[医药卫生]