Interaction mechanism and influence between fatty acid oxidation in trophoblast cells and p38MAPK signal transduction pathway of severe preeclampsia / 中华妇产科杂志

ABSTRACT

Objective To investigate the effects of expression of mitochondria long-chain fatty acid oxidative enzyme (long-chain 3 hyroxyacyl CoA dehydrogenase,LCHAD) and p38 mitogen activated proteinkinase (p38MAPK) signal transduction pathway in severe preeclampsia.Methods Serum-free trophoblast cells cultured in vitro were stimulated by early onset severe preeclampsia serum (E-PE group),late onset severe preeclampsia serum (L-PE group),HELLP syndrome serum (HELLP group),and normal pregnancy serum (NP group) respectively; each group was added DMEM/F12 medium,reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (NADPH-Ⅰ) and p38 MAPK inhibitor (p38-Ⅰ)to stimulate cells.Expression of mRNA and protein of LCHAD in trophoblast cells were detected by real-time PCR and western blot.Results (1) The expression of mRNA of LCHAD:the level of mRNA of LCHAD in NP+DMEM,E-PE + DMEM,E-PE + NADPH-Ⅰ,E-PE + p38-Ⅰ,L-PE + DMEM,L-PE + NADPH-Ⅰ,L-PE + p38-Ⅰ and HELLP + DMEM,HELLP + NADPH-Ⅰ,HELLP + p38-Ⅰ groups were 1.00 ± 0.03,0.14 ±0.08,0.95 ±0.20,1.43±1.02,0.37 ±0.18,1.51 ±0.36,1.60 ±0.31,0.10 ±0.04,0.49 ±0.10,0.44 ± 0.21,respectively.The relative expressions of mRNA of LCHAD were significantly reduced in E-PE + DMEM,L-PE + DMEM and HELLP + DMEM groups compared with the NP + DMEM group (P ＜0.05).Compared with the NP groups,the relative expressions of mRNA of LCHAD were significantly increased in L-PE + NADPH-Ⅰ and L-PE + p38-Ⅰ group (P ＜ 0.05),while reduced in HELLP groups (P ＜0.05).(2) The expression of protein of LCHAD:the relative expressions of protein of LCHAD in NP +DMEM,E-PE + DMEM,E-PE + NADPH-Ⅰ,E-PE + p38-Ⅰ,L-PE + DMEM,L-PE + NADPH-Ⅰ,L-PE +p38-Ⅰ and HELLP + DMEM,HELLP + NADPH-Ⅰ,HELLP + p38-Ⅰ groups were 19.4 ± 2.2,10.7 ± 1.1,17.9±3.3,19.1 ±2.9,16.4 ±2.3,20.3 ±2.3,20.9 ±4.3,12.4 ±2.3,17.6 ±2.6,17.7 ±2.0 respectively.Compared with the NP groups,the protein expressions of LCHAD were significantly remarkably reduced in E-PE + DMEM,L-PE + DMEM and HELLP groups (P ＜ 0.05).Compared with the DMEM groups,the protein expressions of LCHAD were significantly increased in NADPH-Ⅰ and p38-Ⅰ groups of E-PE,L-PE and HELLP groups (P ＜ 0.05).Conclusions These studies demonstrate that long chain fatty acid oxidation was involved in the pathogenesis and development of preeclampsia.The expressions of gene and protein of LCHAD were remarkably affected by early onset severe preeclampsia and HELLP syndrome.NADPH-Ⅰ and p38-Ⅰ may allay the disorder of fatty acid oxidation.p38MAPK signal transduction pathway may contributed in this process.