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早发型子痫前期样改变中脂肪酸氧化与氧化应激的关系
其他题名Interaction of fatty acid oxidation with oxidative stress in preeclampsia-like mouse model at multiple stages of gestation
孙敏娜; 杨孜; 马瑞琼
关键词子痫前期 L-chad 氧化应激 Pre-eclampsia L-chad Oxidative Stress
刊名中华医学杂志
2011
DOI10.3760/cma.j.issn.0376-2491.2011.33.010
91期:33页:2343-2347
收录类别中国科技核心期刊 ; 中文核心期刊 ; CSCD
文章类型Journal Article
摘要目的 通过建立不同妊娠阶段子痫前期样鼠模型以及饮食改变,研究早发型子痫前期样改变中脂肪酸氧化与氧化应激间的相互关系.方法 对C57BL/6J野生型(WT)孕鼠皮下注射左硝基精氨酸甲酯建立早中晚不同孕期时段发病的子痫前期样模型(L-NAME组),设立相应血压正常生理盐水组(NS组).将以上各组再分两个亚组:高脂饲料组(HF组)及标准饲料组(SC组),每组6只鼠.分别于孕1 d起饲喂.同法选取apoE-/-孕鼠作为基因型对照.进行动物模型鉴定;于孕中、晚期进行标本采集.采用RT-PCR、Western Blot技术检测胎盘组织中长链三羟基酰基辅酶A脱氢酶(LCHAD)、p47phox、p38MAPK、COX-2基因及蛋白水平变化.结果 早、中期WT、apoE-/-L-NAME组胎盘内LCHAD基因及蛋白表达明显降低(P<0.05);早、中期WT-HF+L-NAME组及apoE-/--HF+L-NAME组比相应SC组LCHAD基因及蛋白表达也有降低趋势.在早、中期WT及apoE-/--L-NAME组显示胎盘中p47phox、COX-2基因及蛋白表达水平明显升高(P<0.05);WT、apoE-/-孕鼠中HF+L-NAME组的p47phox、COX-2基因及蛋白表达水平比相应SC+L-NAME组高(P<0.05);WT各组与相应apoE-/-各组间进行基因型比较,apoE-/-组的p47phox、COX-2的基因及蛋白水平表达较高(P<0.05).p38MAPK在各组间表达差异无统计学意义(P>0.05).LCHAD与p47phox、COX-2的基因及蛋白水平表达呈负相关性(P<0.05);p47phox与COX-2的基因及蛋白水平呈显著正相关性(P<0.05).结论 不良因素诱发的孕鼠子痫前期样改变,存在脂肪酸氧化代谢关键酶LCHAD障碍,并且发病越早,代谢障碍越明显;WT、apoE-/-早中期子痫前期样改变孕鼠均显示存在一定的氧化应激与炎症损伤;给予高脂饮食可以加重已发生子痫前期样改变孕鼠p47phox及COX-2的表达,apoE-/-孕鼠氧化应激程度更为明显. 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.
语种中文
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文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/69992
专题北京大学第三临床医学院_妇产科
作者单位北京大学第三医院妇产科,100191
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孙敏娜,杨孜,马瑞琼. 早发型子痫前期样改变中脂肪酸氧化与氧化应激的关系[J]. 中华医学杂志,2011,91(33):2343-2347.
APA 孙敏娜,杨孜,&马瑞琼.(2011).早发型子痫前期样改变中脂肪酸氧化与氧化应激的关系.中华医学杂志,91(33),2343-2347.
MLA 孙敏娜,et al."早发型子痫前期样改变中脂肪酸氧化与氧化应激的关系".中华医学杂志 91.33(2011):2343-2347.
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