Li Zhi-Min, Zhao Yun, Chen Qian, Zou Li, Wang Ze-Hua
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zhonghua Fu Chan Ke Za Zhi. 2008 Aug;43(8):584-8.
To investigate the relationship between neurokinin B (NKB), endothelin-1 (ET-1) and the pathogenesis of hypertensive disorder complicating pregnancy (HDCP).
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.
(1) At 10 - 14, 20 - 24, and 30 - 34 gestational weeks, the plasma levels of NKB and ET-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) microg/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) microg/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).
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.
探讨神经激肽B(NKB)、内皮素-1(ET-1)与妊娠期高血压疾病(HDCP)发病机制之间的关系。
选取2005年3月至7月在华中科技大学同济医学院附属协和医院妇产科进行产前检查的22例HDCP患者作为研究对象,其中妊娠期高血压12例(妊娠期高血压组),子痫前期10例(子痫前期组);同期选取22例正常孕妇作为对照组。采用酶联免疫吸附测定技术检测三组孕妇不同孕周母血中NKB和ET-1水平,免疫组织化学SP法检测胎盘组织中NKB的表达及定位,逆转录聚合酶链反应(RT-PCR)法检测胎盘组织中NKB和ET-1的mRNA表达。
(1)子痫前期组孕10~14、20~24、30~34周母血中NKB水平分别为(35.6±5.2)、(17.9±4.3)、(39.5±4.3)μg/L,ET-1水平分别为(22.7±3.6)、(47.1±3.3)、(27.5±3.5)μg/L;对照组孕10~14、20~24、30~34周母血中NKB水平分别为(22.9±3.3)、(10.7±5.3)、(30.2±3.4)μg/L,ET-1水平分别为(13.2±4.1)、(34.6±4.3)、(16.6±4.8)μg/L。子痫前期组与对照组比较差异有统计学意义(P<0.05),妊娠期高血压组与对照组比较差异无统计学意义(P>0.05)。(2)三组胎盘组织均可见NKB蛋白免疫组化染色阳性,位于绒毛合体滋养层细胞、绒毛血管内皮细胞及间质细胞胞质内,以绒毛合体滋养层细胞为主。子痫前期组胎盘组织中NKB表达水平为(0.244±0.020),明显高于对照组(0.160±0.012),两组比较差异有统计学意义(P<0.05);妊娠期高血压组胎盘组织中NKB表达水平为(0.162±0.019),与对照组比较差异无统计学意义(P>0.05)。(3)子痫前期组胎盘组织中NKB mRNA转录水平为(0.97±0.36),ET-1 mRNA转录水平为(0.90±0.36),均明显高于对照组(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);妊娠期高血压组胎盘组织中NKB mRNA转录水平为(0.8±0.40),ET-1 mRNA转录水平为(0.70±0.32),与对照组比较差异无统计学意义(P>0.05)。(4)子痫前期患者母血中NKB与ET-1水平呈明显正相关(r=0.79,P<0.05)。
子痫前期患者母血中NKB和ET-1水平在临床症状出现前即孕早期(孕10~14周)明显升高,母血中NKB和ET-1水平变化与HDCP发病机制密切相关。