在孕早期子痫前期样小鼠中，一氧化氮合酶的抑制降低了脂肪酸的氧化。

Inhibition of nitric oxide synthase lowers fatty acid oxidation in preeclampsia-like mice at early gestational stage.

机构信息

Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.

出版信息

Chin Med J (Engl). 2011 Oct;124(19):3141-7.

PMID:22040569

Abstract

BACKGROUND

Preeclampsia is one of hypertensive disorders in pregnancy. It is associated with abnormal lipid metabolism, including fatty acid oxidation metabolism. Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) plays an indispensable role in the oxidation of fatty acids. It has been reported that nitric oxide (NO) is one of the regulatory factors of the fatty acid oxidation pathway. The aim of this research was to investigate whether the nitric oxide synthase (NOS) inhibitor L-NAME may cause down-regulation of LCHAD in the pathogenesis of preeclampsia.

METHODS

Pregnant wild-type (WT) mice were treated with L-NAME or normal saline (NS) during gestation days 7 - 18 (early group), days 11 - 18 (mid group) and days 16 - 18 (late group), and apoE-/- mice served as a control. Systolic blood pressure (SBP), urine protein, feto-placental outcome, plasma lipid levels and NO concentrations were measured, and the expression of mRNA and protein for LCHAD in placental tissue were determined by real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively.

RESULTS

In WT and apoE-/- mice, SBP and urinary protein increased following L-NAME injection. Fetal and placental weights and NO concentrations were reduced and total cholesterol, triglycerides and free fatty acid levels were increased in early and mid L-NAME groups in WT and apoE-/- mice, compared with the NS group. There was no significant difference between the late L-NAME group and NS group. RT-PCR and Western blotting analysis showed that the mRNA and protein levels of LCHAD expression were significantly down-regulated in the early and mid L-NAME groups but not in the late L-NAME group in the WT and apoE-/- mice compared with the corresponding NS groups.

CONCLUSIONS

Inhibition of NO in early and mid gestation in mice may cause hyperlipidemia and suppression of fatty acid oxidation, whereas preeclampsia-like conditions in late gestation may be a maternal vascular response to inhibition of NO.

摘要

背景

子痫前期是妊娠高血压疾病之一，与脂代谢异常有关，包括脂肪酸氧化代谢。长链 3-羟基酰基辅酶 A 脱氢酶（LCHAD）在脂肪酸氧化中起着不可或缺的作用。据报道，一氧化氮（NO）是脂肪酸氧化途径的调节因子之一。本研究旨在探讨一氧化氮合酶（NOS）抑制剂 L-NAME 是否会导致子痫前期发病过程中 LCHAD 的下调。

方法

在妊娠第 7-18 天（早期组）、第 11-18 天（中期组）和第 16-18 天（晚期组），用 L-NAME 或生理盐水（NS）处理妊娠野生型（WT）小鼠，apoE-/- 小鼠作为对照。测量收缩压（SBP）、尿蛋白、胎-胎盘结局、血浆脂质水平和 NO 浓度，并通过实时聚合酶链反应（RT-PCR）和 Western 印迹分别测定胎盘组织中 LCHAD 的 mRNA 和蛋白表达。

结果

在 WT 和 apoE-/- 小鼠中，注射 L-NAME 后 SBP 和尿蛋白增加。与 NS 组相比，WT 和 apoE-/- 小鼠的早期和中期 L-NAME 组的胎儿和胎盘重量以及 NO 浓度降低，总胆固醇、甘油三酯和游离脂肪酸水平升高。晚期 L-NAME 组与 NS 组无显著差异。RT-PCR 和 Western 印迹分析显示，与相应的 NS 组相比，WT 和 apoE-/- 小鼠的早期和中期 L-NAME 组的 LCHAD 表达的 mRNA 和蛋白水平显著下调，但晚期 L-NAME 组无明显变化。