氧化低密度脂蛋白及其受体与子痫前期发病的关系

目的 探讨氧化低密度脂蛋白(oxLDL)及血凝集素样氧化低密度脂蛋白受体1(LOX-1)与子痫前期发病的关系.方法 选择2007年6月至2008年1月在青岛大学医学院附属医院产科住院分娩的子痫前期孕妇73例,其中轻度子痫前期孕妇35例(轻度子痫前期组),重度子痫前期孕妇38例(重度子痫前期组).选取同期正常晚期妊娠妇女45例为对照组.采用酶联免疫吸附试验检测各组孕妇血浆中oxLDL水平;采用RT-PCR、蛋白印迹法分别检测各组孕妇胎盘组织中LOX-1 mRNA及蛋白表达水平;采用RT-PCR检测各组孕妇胎盘组织中半胱氨酸天门冬氨酸蛋白酶-3(caspase-3)mRNA表达水平.结果 (1)轻度及重度子痫前期组孕妇血浆中oxLDL水平分别为(0.42±0.11)及(0.68±0.12)mg/L,明显高于对照组的(0.35±0.14)mg/L,差异有统计学意义(P<0.01);重度子痫前期组又明显高于轻度子痫前期组(P<0.01).(2)轻度及重度子痫前期组孕妇胎盘组织中LOX-1mRNA表达水平分别为0.70±0.10及0.84±0.08,明显高于对照组的0.58±0.11,差异有统计学意义(P<0.01);重度子痫前期组又明显高于轻度子痫前期组(P<0.01).(3)轻度及重度子痫前期组孕妇胎盘组织中LOX-1蛋白表达水平分别为0.79±0.15及0.90±0.12,明显高于对照组的0.68±0.11,差异有统计学意义(P<0.01);重度子痫前期组又明显高于轻度子痫前期组(P<0.01).(4)轻度及重度子痫前期组孕妇胎盘组织中caspase-3 mRNA表达水平分别为3.82±0.18及5.39±0.14,明显高于对照组的2.19±0.20,差异有统计学意义(P<0.01);重度子痫前期组又明显高于轻度子痫前期组(P<0.01).(5)轻度及重度子痫前期组孕妇血浆中oxLDL水平与胎盘组织中LOX-1 mRNA表达水平呈正相关(r=0.93,P<0.05);胎盘组织中LOX-1 mRNA表达与胎盘组织caspase-3 mRNA表达水平呈正相关(r=0.84,P<0.05).结论 子痫前期孕妇血浆中oxLDL水平升高,并上调胎盘组织中的LOX-1表达水平,从而参与子痫前期的病理生理过程.

Correlation of oxidized low-density lipoprotein and lectin-like oxidized low-density lipoprotein receptor-1 with pre-eclampsia

Objective To investigate the role of oxidized low-density lipoprotein (oxLDL) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-I) in pre-ecalmpsia. Methods From June 2007 to January 2008,73 women with pre-eelampsia who delivered in the Department of Obstetrics, Affiliated Hospital of Qingdao University Medical College,were recruited, including 35 women with mild pre-eclampsia (MPE group) and 38 women with severe pre-eclampsia(SPE group). And 45 healthy pregnant women were taken as control group. Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma concentrations of oxLDL in these women. Semiquantitative RT-PCR and Western blot were used to investigate the expression of LOX-1 mRNA and protein in placenta. The expression of caspase-3 mRNA in placenta was determined using Semiquantitative RT-PCR. Results (1) The plasma concentrations of oxLDL in MPE group ( 0.42 ± 0.11 ) mg/L, SPE group ( 0.68 ± 0.12 ) mg/L, were significantly higher compared with control group (0.35 ± 0.14 )mg/L( P < 0.01 ) and the concentrations of oxLDL in MPE group were significantly higher compared with SPE group (P<0.01 ). (2) The expression of LOX-1 mRNA in placenta of MPE group(0.70 ±0.10) and SPE group(0.84 ±0.08) were significantly higher than that in control group(0.58 ± 0.11 ) ( P<0.01 ) and the expression of LOX-1 mRNA in MPE group was significantly higher than that of SPE group (P<0.01 ). (3) The expression of LOX-1 protein in placenta of MPE group (0.79±0.15 )and SPE group(0.90±0.12) were significantly higher compared with control group(0.68 ±0.11)( P<0.01 ), while the expression of LOX-1 protein of MPE group was significantly higher compared with SPE group (P <0.01 ). (4) The expression of caspase-3 mRNA in placenta of MPE group(3.82± 0.18) and SPE group(5.39±0.14) were significantly higher than that in control group(2.19±0.20) (P <0.01 ), and the expression of caspase-3 mRNA in MPE group was significantly higher than that of SPE group (P<0.01 ). (5) In pre-eclampsia groups, the levels of LOX-1 mRNA in placenta were positively correlated with the plasma concentrations of ox LDL ( r=0.93, P<0.05 ), and caspase-3 mRNA expression were positively correlated with the expression of LOX-1 mRNA in placenta( r=0.84, P<0.05). Conclusion Increased levels of oxLDL in plasma may induce excess expression of LOX-1 in placenta, which may be involved in the pathophysiological processes of pre-eclampsia.