Correlation between severe preeclampsia and abnormal expression of long-chain fatty acid oxidative enzyme

目的 探讨重度子痫前期与参与长链脂肪酸氧化的长链三羟基酰基辅酶A脱氢酶(LCHAD)mRNA和蛋白表达异常的相关性.方法 通过体外无血清培养胎盘滋养细胞,然后分为4组,分别用正常妊娠孕妇(NP组)、早发型重度子痫前期(E-PE组)、晚发型重度子痫前期(L-PE组)、重度子痫前期伴发HELLP综合征(HEILP组)患者血清刺激胎盘滋养细胞.采用实时荧光定量PCR和蛋白印迹法检测各组LCHAD基因和蛋白的表达.结果 (1)LCHAD的mRNA表达变化:NP、E-PE、L-PE及HELLP组LCHAD mRNA相对表达量分别为1.00±0.00、3.08±0.22、1.62±0.23、3.36±0.18.与NP组比较,E-PE、L-PE及HELLP组LCHAD的mRNA相对表达量均明显降低(P＜0.05);与L-PE组相比较,E-PE、HELLP组LCHAD的mRNA相对表达量也有明显降低(P＜0.05);而E-PE与HELLP组两组间LCHAD的mRNA表达差异无统计学意义(P＞0.05).(2)LCHAD蛋白表达变化:NP、E-PE、L-PE及HELLP组LCHAD/β-肌动蛋白比率分别为4.94±0.02、2.93±0.13、4.14±0.06、2.80±0.09.与NP组比较,E-PE、L-PE及HELLP组LCHAD蛋白表达均明显降低(P＜0.05);E-PE、HELLP组LCHAD蛋白表达比L-PE组都有明显降低,差异有统计学意义(P＜0.05);而E-PE与HELLP组两组间差异无统计学意义(P＞0.05).结论 重度子痫前期对胎盘滋养细胞中LCHAD的基因蛋白表达异常存在一定的影响,其中以早发型重度子痫前期和HELLP综合征的影响更为明显.脂肪酸氧化与子痫前期发生发展的相互影响和作用机制值得深入探讨.Objective To explore the correlation between severe preeclampsia and abnormal expression of long-chain 3-hyroxyacyl-CoA dehydrogenase (LCHAD). Methods Serum-free trophoblast cells cultured in vitro were divided into 4 groups under the stimulations of normal pregnancy serum ( NP group), early onset severe preeclampsia serum (E-PE group), late onset severe preeclampsia serum (L-PE group) and HELLP ( hemolysis, elevated liver enzymes & low platelets) syndrome serum ( HELLP group)respectively. The expressions of mRNA and protein of LCHAD in trophoblast cells were detected by real-time polymerase chain reaction (PCR) and Western blot. Result ( 1 ) Expression of LCHAD mRNA: the relative expressions of mRNA of LCHAD in NP, E-PE, L-PE and HELLP groups were 1.00 ±0.00, 3.08 ±0.22, 1.62 ± 0. 23 and 3.36 ± 0. 18 respectively. The relative expressions of LCHAD mRNA were significantly reduced in the E-PE, L-PE and HELLP groups versus the NP group ( P ＜ 0. 05 ). Compared with the L-PE group, the gene expressions of LCHAD significantly decreased in the E-PE and HELLP groups (P ＜0.05 ) while no significant difference was found between the E-PE and HELLP groups (P ＞ 0. 05 ).(2) Expression of LCHAD protein: the relative expressions of LCHAD protein were 4.94 ±0.02, 2.93 ±0. 13, 4. 14 ±0. 06 and 2.80 ±0.09 in the NP, E-PE, L-PE and HELLP groups respectively. The protein expressions of LCHAD were remarkably reduced in the E-PE, L-PE and HELLP groups versus the NP group (P ＜ 0.05 ). The expressions of LCHAD protein remarkably decreased in the E-PE and HELLP groups versus the L-PE group (P ＜0.05) while no significant difference was found between the E-PE and HELLP groups (P ＞ 0. 05 ). Conclusion Long chain fatty acid oxidation is involved in the pathogenesis and development of preeclampsia. The expressions of LCHAD gene and protein are remarkably affected by early onset severe preeclampsia and HELLP syndrome. The interacting mechanism and influence between fatty acid oxidation and the development of preeclampsia are worth further exploring.国家自然科学基金; 北京市自然科学基金PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)0292026-20299