[Interaction of fatty acid oxidation with oxidative stress in preeclampsia-like mouse model at multiple stages of gestation].
OBJECTIVE
To investigate the interactions of fatty acid oxidation with oxidative stress on the preeclampsia (PE)-like development by establishing murine models at multiple stages of gestation.


METHODS
Wild-type (WT) mice were injected subcutaneously with nitric oxide synthase (NOS) inhibitor L-arginine methyl ester (L-NAME, 50 mg×kg(-1)×d(-1)) to establish PE-like model (L-NAME group) at early, middle and late pregnant periods respectively. Normal saline (NS group) was injected simultaneously as a control. All groups were divided into subgroups, standard chow group (SC) and high-fat diet group (HF). From Day 1 of pregnancy, all groups were fed simultaneously. ApoE(-/-) pregnant mice were selected as a control group. Identification of mice model and the expressions of mRNA and protein of LCHAD, p47phox, p38MAPK and COX-2 were confirmed by RT-PCR (reverse transcription-polymerase chain reaction) and Western blot respectively. Data were analyzed statistically.


RESULTS
The expressions of mRNA and protein of LCHAD significantly decreased in early and middle L-NAME groups in both apoE(-/-) and WT mice (P < 0.05). The expressions of mRNA and protein of LCHAD in the HF groups were lower than the SC groups. The changes were marked in the early HF + L-NAME subgroup in apoE(-/-) mice (P < 0.05). As compared with other groups, the placental expressions of mRNA and protein of p47phox and COX-2 markedly increased in the early and middle L-NAME subgroups in apoE(-/-) mice (P < 0.05), especially in early and middle HF + L-NAME subgroups in apoE(-/-) mice (P < 0.05). ApoE(-/-) mice had a higher expression than that of WT groups (P < 0.05). The expressions of mRNA and protein of p38MAPK showed no differences among all groups. Correlation analysis showed a negative correlation between gene and protein expressions of LCHAD and p47phox, COX-2 (P < 0.05). There was significantly positively correlated between the expression of p47phox, COX-2 and protein (P < 0.05).


CONCLUSIONS
The PE-like symptoms have fatty acid oxidation dysfunctions. There is a lower expression of LCHAD. The earlier its onset, the more obvious dysfunctions. In early and middle L-NAME groups, oxidative stress and inflammatory injury occur in both apoE(-/-) and WT mice. A high-fat diet may aggravate the level of oxidative stress especially in PE-like apoE(-/-) murine model.
Department of Obstetrics & Gynecology, Peking University Third Hospital, Beijing 100191, China.
Min-Na
MN
Sun
Zi
Z
Yang
Rui-Qiong
RQ
Ma
D000818:Animals; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011225:Pre-Eclampsia / Q000235:genetics; D011247:Pregnancy
D005227:Fatty Acids; D019331:NG-Nitroarginine Methyl Ester