神经激肽B和内皮素1与妊娠期高血压疾病发病的关系

Relationship between neurokinin B and endotheUn-I and hypertensive disorders complicating pregnancy

目的探讨神经激肽B（NKB）和内皮素1（ET-1）与妊娠期高血压疾病（HDCP）发病的关系。方法选择2005年3—7月在华中科技大学同济医学院附属协和医院妇产科行产前检查的22例HDCP孕妇作为研究对象，其中，妊娠期高血压12例为妊娠期高血压组，子痫前期10例为子痫前期组；同期22例正常孕妇为对照组。分别采用酶联免疫吸附试验测定3组不同孕周孕妇血浆中NKB和ET-1的水平，采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接法（sP）检测NKB在胎盘组织中的定位和表达，采用RT—PCR技术检测胎盘组织中的NKBmRNA和ET-1 mRNA表达。结果（1）子痫前期组孕10—14周、孕20一24周、孕30～34周孕妇血浆中NKB和ET-1的水平分别为（35．6±5．2）、（17．9±4．3）pg／L，（39．5±4．3）、（22．7±3．6）ug／L，（47．1±3．3）、（27．5±3．5）ug／L；对照组分别为（22．9±3．3）、（10．7±5．3）ug／L，（30．2±3．4）、（13．2±4．1）ug/L，（34．6±4．3）、（16．6±4．8）ug／L，两组分别比较，差异均有统计学意义（P〈0．05）；妊娠期高血压组与对照组比较，差异均无统计学意义（P〉0．05）。（2）各组孕妇胎盘组织中的绒毛合体滋养细胞、绒毛血管内皮细胞及间质细胞的胞质内均可观察到NKB蛋白阳性染色颗粒，其中以合体滋养细胞的分布为主。子痫前期组胎盘组织中的NKB蛋白表达水平（0．244±0．020）显著高于对照组（0．160±0．012），两组比较，差异有统计学意义（P〈0．05）。而妊娠期高血压组NKB蛋白表达水平（0．162±0．019）与对照组比较．差异无统计学意义（P〉0．05）。（3）子痫前期组孕妇胎盘组织中的NKBmRNA（0．97±0．36）和ET-1 mRNA（0．90±0．36）表达水平显著高于对照组（分别为0．78±0．54、0．65±0．47），两组比较，差异有统计学意义（P〈0．05）；而妊娠期高血压组（分别为0．80±0．40、0．70±0．32）与对照组比较，差异无统计学意义（P〉0．05）。（4）子痫前期组孕妇血浆中NKB水平与ET-1水平呈正相关关系（r=0．79，P〈0．05）。结论子痫前期患者在孕早期（孕10—14周）临床症状出现之前，其血浆中NKB和ET-1水平即已显著升高，胎盘组织中NKB和ET-1表达水平也明显升高。子痫前期患者体内NKB和ET-1水平变化与HDCP的发病密切相关。

Objective To investigate the relationship between neurokinin B （ NKB）, endothelin-1 （ET-1） and the pathogenesis of hypertensive disorder complicating pregnancy （HDCP） . Methods 22 HDCP, who received antenatal examination in the Department of Obstetrics and Gynecology of Union Hospital of Tongji Medical College in Huazhong University of Science and Technology from March to July in 2005, were selected for the study, including 12 gestational hypertension （gestational hypertension group） and 10 preeclampsia （preeclamptic group）; 22 normal pregnant women in the same period were served as control. At different gestational weeks, maternal plasma levels of NKB and ET-1 in three groups were detected by enzyme-linked immunoassay technique, the expression and location of NKB in placenta were examined by immunohistochemical SP, and mRNA expressions of NKB and ET-1 in placenta were measured with RT-PCR method. Results （ 1 ） At 10 - 14, 20 - 24, and 30 - 34 gestational weeks, the plasma levels of NKBandET-1 in preeclamptic group were （35.6 ±5.2）, （17.9 ±4.3）, （39.5 ±4.3）, （22.7± 3.6） , （47. 1 ±3.3） and （27. 5 ±3.5） ug/L, respectively; in the control group they were （22. 9 ±3.3）, （10.7±5.3）, （30.2±3.4）, （13.2±4.1）, （34.6 ±4.3） and （16.6 ±4.8）ug/L, respectively. There was a significant difference between preeclamptic group and control group （ P 〈 0. 05 ）, while there was no significant difference between gestational hypertension group and control group （ P 〉 0. 05 ）. （ 2 ） Immunohistochemical staining for NKB protein was observed in all groups and was located in the villous syncytiotrophoblast and villous vascular endothelial cells as well as cytoplasm of stromal cells, mostly located in villous syncytiotrophoblast. The expressions of NKB in placenta of preeclamptic group （0. 244 ± 0. 020） was significantly higher than that in control group （0. 160 ±0. 012）, with a significant difference between the two groups （ P 〈 0. 05 ）. However, there was no significant difference between gestational hypertension group （0. 162 ±0. 019） and control group （P 〉 0. 05 ）. （3） The transcription levels of the NKB mRNA （0. 97 ±0. 36） and ET-1 mRNA （0. 90 ±0. 36） in preeclamptic placentas were both significantly higher than those in control groups （0. 78 ± 0. 54, 0. 65 ± 0. 47, respectively ）, with a significant difference between the two groups（ P 〈0. 05 ）. But there was no significant difference between gestational hypertension group （0. 80 ± 0. 40, 0. 70 ± 0. 32, respectively） and control group （ P 〉 0. 05 ）. （4） There was an evident positive correlation between plasma NKB and ET-1 levels in preeclampsia （ r = 0. 79, P 〈 0. 05 ） . Conclusions The significantly increased maternal plasma levels of NKB and ET-1 of patients with preeclampsia occur at early pregnancy （10 - 14 gestational weeks） before the onset of clinical symptoms. The change of maternal plasma levels of NKB and ET-1 is closely related to pathogenesis of HDCP.