内源性一氧化氮合酶抑制物及其水解酶变化与子痫前期发病的关系

Relationship between changes of endogenous nitric oxide synthase inhibitor and hydrolase and initiation of pre-eclampsia

目的探讨子痫前期孕妇血浆内源性一氧化氮合酶抑制物——非对称性二甲基精氨酸（ADMA）的水平变化及胎盘组织中一氧化氮合酶抑制物水解酶——二甲基精氨酸二甲胺水解酶2（DDAH-2）的表达变化与子痫前期发病的关系。方法选择2004年1月至2005年1月在广州医学院第三附属医院住院分娩的子痫前期孕妇30例（子痫前期组），以同期正常晚期妊娠妇女10例（正常妊娠组）为对照。采用高效液相色谱（HPLC）分析法测定两组孕妇血浆ADMA水平；采用荧光定量PCR技术检测两组孕妇胎盘组织中DDAH-2 mRNA的表达。结果（1）血浆ADMA水平：子痫前期组孕妇血浆ADMA水平为（18．0±7．2）mg／L，高于正常妊娠组的（10．3±1．7）mg／L，两组比较，差异有统计学意义（P〈0．01）；子痫前期组中，发病孕周〈34周者血浆ADMA水平为（22．0±7．0）mg／L，显著高于发病孕周≥34周者的（12．7±2．8）mg/L，两者比较，差异也有统计学意义（P〈0．01）。（2）胎盘组织DDAH-2mRNA的表达量：子痫前期组胎盘组织中DDAH-2 mRNA的表达量为1×10^（5.23±0.45）copy／μl，显著低于正常妊娠组的1×10^（5.65±0.08）copy／μl，两组比较，差异有统计学意义（P〈0．01）；子痫前期组中，发病孕周〈34周者胎盘组织DDAH-2mRNA表达量为1×10^（5.02±0.46）copy／μl，显著低于发病孕周≥34周者的1×10^（5.61±0.19）copy／μl，两者比较，差异也有统计学意义（P〈0．01）。结论胎盘组织中DDAH-2mRNA的低表达与血浆ADMA水平的升高，可能与子痫前期的发病有关。

Objective To investigate the role of dimethylarginine dimethylaminohydrolase-2（DDAH-2）/asymmetric dimethylarginine （ADMA） in pathophiology of preeclampsia by detecting expression of DDAH-2 in placenta and serum plasma ADMA. Methods From Jan. 2004 to Jan. 2005, 30 preeelampsia patients （PE group ） were chosen in the Third Affiliated Hospital, Guangzhou Medical College matched with 10 normal third trimester women as control （control group）. The placental DDAH-2 mRNA expression was detected by fluorescence quantitative polymerase chain reaction （FQ-PCR） and the plasma concentration of ADMA was determined by high performance liquid chromatography （HPLC）. Results （ 1 ） The level of ADMA in PE group was significantly higher that than of control group [ （ 18.0± 7.2）mg/L vs. （ 10. 3 ± 1.7） mg/L, P 〈0. 011- The expression level of ADMA in preeclampsia occurring before 34 gestatinal weeks was significantly higher than that of preeclampsia occurring after 34 gestational weeks [（22.0±7.0） mg/L vs. （12.7±2.8） mg/L, P〈0.01]. （2） The Placental DDAH-2 mRNA expression in preeclampsia patients was remarkably lower than that of control group [ 1 × 10^（5. 23 ±0. 45） copy/μl vs. 1 × 10^（5.65±0.08） copy/μl,P 〈 0. 01 1. The Placental DDAH-2 mRNA in preeclampsia occurring before 34 gestatinal weeks was significantly lower than that of preeclampsia occurring after 34 gestational weeks [1 ×10^（5.02±0.46）copy/μl vs. 1 ×10^（5.61±0.19）copy/μl, P〈0.01]. Conclusion Our results suggested that low expression of DDAH-2 in placenta and increased serum ADMA level might confer the susceptibility to preeelampsia.