孕妇血清及其新生儿脐血、胎盘组织中脂肪型脂肪酸结合蛋白表达变化与子痫前期发病的关系

Expression and significance of adipocyte fatty acid-binding protein in placenta, serum and umbilical cord blood in preeclampsia

目的 探讨孕妇血清及其新生儿脐血中脂肪型脂肪酸结合蛋白（FABP4）水平、胎盘组织中FABP4 mRNA的表达变化在子痫前期发病中的作用.方法 选择2008年12月-2009年10月在福建省妇幼保健院产科住院分娩的60例重度子痫前期孕妇,按发病时孕周不同分为早发型子痫前期组（发病时孕周≤34周）和晚发型子痫前期组（发病时孕周〉34周）各30例;另选同期正常晚期孕妇60例,根据孕周不同分为早发型对照组（孕周≤34周）和晚发型对照组（孕周〉34周）各30例.采用酶联免疫吸附试验（ELISA）检测孕妇血清FABP4、空腹血糖（FPG）、空腹胰岛素（FINS）及新生儿脐血FABP4水平;采用稳态模型评估法计算胰岛素抵抗指数（HOMA-IR）;采用逆转录（RT）PCR技术检测胎盘组织中FABP4 mRNA的表达;记录临床相关指标,包括孕妇入院时体质指数（BMI）、收缩压（SP）、舒张压（DP）及平均动脉压（MAP）、血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、肌酐（Cr）、尿酸（UA）、肾小球滤过率（GFR）、24 h尿蛋白定量和新生儿出生体质量.结果 （1）早发型及晚发型子痫前期组孕妇血清中FABP4水平分别为（176±9）及（170±9）ng/L,早发型及晚发型对照组分别为（81±13）及（94±15）ng/L,分别比较,差异均有统计学意义（P〈0.05）.（2）早发型及晚发型子痫前期组孕妇血清FINS、HOMA-IR水平分别为（21.9±4.3）mU/L、5.1±1.7及（22.6±4.0）mU/L、4.9±1.5,分别比较,差异均有统计学意义（P〈0.05）.（3）早发型及晚发型子痫前期组孕妇胎盘组织中FABP4 mRNA的表达水平分别为3.17±0.89及2.97±0.72,均高于晚发型对照组的1.00±0.28,分别比较,差异均有统计学意义（P〈0.05）;但早发型子痫前期组与晚发型子痫前期组比较,差异无统计学意义（P〉0.05）.（4）早发型及晚发型子痫前期组新生儿脐血中FABP4水平分别为（92±10）及（100±8）ng/L,均低于晚发型对照组的（141±18）ng/L,分别比较,差异均有统计学意义（P〈0.05）.早发型子痫前期组、晚发型子痫前期组及晚发型对照组新生儿出生体质量两两比较,差异均有统计学意义（P〈0.05）.相关性分析结果显示,脐血FABP4水平与孕妇血清FABP4及胎盘组织中FABP4 mRNA表达水平均呈明显负相关（r分别为-0.882、-0.678,P〈0.05）,与新生儿出生体质量呈明显正相关（r=0.728,P〈0.05）.（5）早发型及晚发型子痫前期组孕妇血清中FABP4水平与胎盘组织中FABP4 mRNA表达水平均呈明显正相关（r分别为0.609、0.403,P〈0.05）,与血TG（r分别为0.702、0.562）,FINS（r分别为0.528、0.423）,HOMA-IR（r分别为0.566、0.519）,Cr（r分别为0.443、0.523）,UA（r分别为0.438、0.413）均呈明显正相关（P〈0.05）,而与血HDL（r分别为-0.539、-0.498）,GFR（r分别为-0.717、-0.778）均呈明显负相关（P〈0.05）.结论 子痫前期孕妇血清FABP4水平及胎盘组织中FABP4 mRNA表达水平均明显升高,且两者呈明显正相关.提示FABP4水平升高可能是子痫的期发病的重要因素之一,而胎盘组织中FABP4 mRNA表达水平升高可能是导致子痫的期孕妇血清FABP4水平升高的主要原因.

Objective To investigate the change of adipocyte fatty acid-binding protein（FABP4） in maternal serum and umbilical cord blood and FABP4 mRNA placental expression in patients with preeclampsia（PE）. Methods A total of 60 women with PE and 60 normal pregnant women as control participated in this study. All are admitted to Fujian Maternity and Children Health Hospital for delivery from December 2008 to October 2009. Patients with PE were divided into early-onset group （n = 30, presented at ≤34 weeks of gestation） and late-onset group（n = 30, presented at 〉 34 weeks of gestation）, with 30 normal pregnant women as early control group（≤34 weeks of gestation） and 30 as late control group（〉34 weeks of gestation）. Enzyme-linked immunosorbent assay （ELISA） was used to detect FABP4,fasting serum glucose,fasting insulin（FINS） in maternal serum and FABP4 in umbilical cord blood. Real-time fluorescent quantitative revere transcription PCR was used to detect placental FABP4 mRNA expression. Furthermore,clinical and biochemical parameters were recorded, such as body mass index（BMI）, systolic pressure（SP）,diastolic pressure （DP）, mean arterial pressure （MAP）, total cholesterol （TC）, triglyceride （TG）, low density lipoprotein （LDL）, high density lipoprotein （HDL）, creatinine （Cr）, uric acid （UA） , glomerular filtration rate （GFR）, 24 hours urine protein in pregnant women and neonatal weight. Results （1） Maternal serum FABP4 was （176 ± 9） ng/L in early-onset PE group and （170 ± 9） ng/L in late-onset PE group, significantly elevated as compared to （81 ± 13） ng/L in early control group and （94 ± 15） ng/L in late control group. （2） Mean maternal FINS, homeostasis model of assessment for insulin resistence index （HOMA-IR） were significantly elevated in the early-onset PE group and late-onset PE group as compared to control groups, respectively. （3） Mean placental FABP4 mRNA expression were significantly elevated in the early-onset PE group and late-onset PE group as compared to late control group. However, no significant difference was found in placental FABP4 mRNA expression between early-onset and late-onset PE groups.（4） Mean umbilical cord blood FABP4 concentrations were significantly decreased in the early-onset PE group and late-onset PE group as compared to late control group. Furthermore, umbilical cord blood FABP4 concentration correlated negatively with maternal serum FABP4 level and placental FABP4 mRNA expression, but positively with neonatal weight. （5） Mean maternal serum FABP4 concentrations correlated positively with placental FABP4 mRNA expression,TG, FINS, HOMA-IR, Cr, UA; and negatively with HDL, GFR. Conclusions Increased FABP4 expression in maternal serum and placenta may be involved in the pathogenesis of preeclampsia. Increased FABP4 mRNA expression in placenta may contribute to high serum FABP4 level in women with PE.