长链脂肪酸线粒体氧化相关酶在不同子痫前期样鼠模型中的变化研究
Mitochondrial long chain fatty acid oxidation related enzyme changes in different preeclampsia-like mouse models
目的通过建立四种不同诱发途径以及不同发病时间的子痫前期样鼠模型，研究长链脂肪酸线粒体氧化相关酶LCHAD及CPTI/II在不同因素子痫前期发病中的变化及其与FFA变化的相关性。方法 采用存在脂代谢遗传因素的ApoC3转基因鼠和存在母体基础疾病的APS鼠、以及经典的L-NAME和LPS方法建立不同诱发途径的子痫前期样改变的鼠模型（ApoC3+NS组，ApoC3+L-NA组，β2GPI组，L-NA组和LPS组，按n=10），以野生型注射生理盐水作为对照组（control组，n=10）。进行模型鉴定，于孕14天和孕18天进行标本取材。比较各组血清游离脂肪酸的变化。采用实时荧光定量PCR和蛋白印记法分别检测胎盘和肝组织中CPTI/II、LCHAD mRNA和蛋白的表达。结果与对照组比较，14D和18D组血清中FFA除在LPS组中无显著性差异外，在其他实验组均显著增加（P<0.05）。CPTI mRNA和蛋白表达在L-NA组和β2GPI组的肝脏和胎盘组织与对照组比较均显著增加（P<0.05），在ApoC3+L-NA组的肝脏显著增加（P<0.05）。CPTII mRNA和蛋白表达在L-NA组的肝脏和胎盘组织与对照组比较均显著增加（P<0.05），在ApoC3+L-NA组和β2GPI组的肝脏显著增加（P<0.05）。LCHAD mRNA和蛋白表达在ApoC3+NS组、ApoC3+L-NA组和β2GPI组的肝脏和胎盘组织与对照组比较均显著增加（P<0.05），在L-NA组显著降低（P<0.05）。血清FFA水平在各实验组与肝脏CPTI mRNA和蛋白表达呈显著正相关（P<0.05），与CPTII mRNA和蛋白表达无显著相关性。在ApoC3+NS组、ApoC3+L-NA组、L-NA组和LPS组与肝脏LCHAD mRNA和蛋白表达呈显著负相关（P<0.05），在β2GPI组与肝脏LCHAD mRNA和蛋白表达呈显著正相关（P<0.05）。结论不同因素导致的子痫前期样鼠模型中FFA水平与LCHAD和CPTI/II基因和蛋白表达水平存在不同的变化及相关性。提示长链脂肪酸氧化障碍可能发生在长链脂肪酸进入线粒体氧化循环过程中的不同环节，并且其在不同因素诱发的子痫前期样鼠模型中的影响和作用不同。
ims We studied the relationship between LCHAD, carnitine palmitoyltransferase (CPT) I and II and FFA in different preeclampsia-like models.Methods Injection of Nw-nitro-L-arginine-methyl ester (L-NA) or lipopolysaccharide (LPS) established classic preeclampsia models, antiphospholipid syndrome model with β2 glycoprotein I (β2GPI) injection, and ApoC3 mice with abnormal fatty acid metabolism (ApoC3+NS and ApoC3+L-NA) were used. Controls were saline injected. At days 14 and 18 of pregnancy, serum FFA were compared and placental and hepatic LCHAD, CPT I and II mRNA and protein were detected using real-time quantitative PCR and western blot.Results Serum FFA levels increased significantly except in LPS, compared to controls (P <0.05). CPT I mRNA and protein increased significantly in the liver and placenta of L-NA and β2GPI and liver of ApoC3+L-NA (P <0.05). CPT II mRNA and protein increased significantly in the liver and placenta of L-NA and the liver of ApoC3+L-NA and β2GPI (P <0.05). LCHAD mRNA and protein increased significantly in the liver and placenta of ApoC3+NS, ApoC3+L-NA and β2GPI, and decreased significantly in L-NA (P <0.05). Serum FFA levels positively correlated with liver CPT I mRNA and protein in all groups (P <0.05) and negatively correlated with liver LCHAD mRNA and protein expression in all groups except in β2GPI group (P <0.05).Conclusions Changes and correlations in FFA levels and LCHAD, CPT I and II were different according to preeclampsia-like models. β-oxidation disorders may occur at different stages.
杨孜、韩怡炜、丁晓燕、于欢
基础医学妇产科学
子痫前期脂肪酸氧化肉毒碱棕榈酰转移酶
Pre-EclampsiaFatty acid oxidationCarnitine Palmitoyltransferase
杨孜,韩怡炜,丁晓燕,于欢.长链脂肪酸线粒体氧化相关酶在不同子痫前期样鼠模型中的变化研究[EB/OL].(2017-04-24)[2025-08-25].http://www.paper.edu.cn/releasepaper/content/201704-364.点此复制
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