作者：王晓君1 ，夏剑清 1 ，侯洁 1 ，张烈民 1 ，王平 1 ，苏勇 1 ，吴文娜 1 ，黄大健 1 ，徐丹 1 ，成慧娟 1 ，薛艳 1 ，徐志平2 ，周晓阳 3

单位：

1.430070 湖北省武汉市，湖北省妇女儿童医院 华中科技大学同济医学院附属湖北妇幼保健院内科　；2.430400 湖北省武汉市中心医院新洲区分院　；3.430060 湖北省武汉市，武汉大学人民医院心血管内科；通信作者：周晓阳，E-mail：xiaoyangzh@whu.edu.cn

关键词：

高血压，妊娠性；拉贝洛尔；硝苯地平；血压；半胱氨酸；脐动脉；血流动力学；对比研究

Keywords：

Hypertension，pregnancy-induced；Labetalol；Nifedipine；Blood pressure；Cysteine；Umbilicalarteries；Hemodynamics；Comparative study

CLC：

R 714.246

DOI：

DOI：10.3969/j.issn.1008-5971.2020.04.013

Funds：

国家自然科学基金资助项目（81370337，81970331）

摘要：

背景　合理控制血压并不能有效降低妊娠期高血压（PIH）患者子痫前期发生风险，而控制 PIH 患者血压的同时最大限度地增加脐动脉血流直接关系到母婴结局，因此探讨 PIH 患者精准控压策略具有重要现实意义。目的　对比拉贝洛尔片与硝苯地平缓释片对 PIH 患者血压、血浆同型半胱氨酸（Hcy）水平、脐动脉血流动力学的影响，以初步探索基于无创血流动力学监测的 PIH 精准控压策略。方法　选取湖北省妇女儿童医院内科及武汉市中心医院新洲区分院内科门诊 2015 年 6 月—2019 年 3 月收治的 PIH 患者 120 例，采用 SPSS 16.0 统计学软件完全随机化设计分组法分为 A 组和 B 组，每组 60 例；另选取同期在湖北省妇女儿童医院进行产检及分娩的健康孕妇 60 例作为对照组。本研究启动降压治疗的血压阈值为≥ 150/100 mm Hg（1 mm Hg=0.133 kPa），以治疗后血压控制在 130~140/80~90mm Hg 为达标。A 组患者口服拉贝洛尔片，B 组患者口服硝苯地平缓释片；两组患者均连续治疗 4 周。比较三组受试者入组次日及 A 组与 B 组患者治疗后收缩压（SBP）、舒张压（DBP）、血浆 Hcy 水平及脐动脉收缩末期血流速度 /舒张末期血流速度比值（S/D）、时间平均流速（VM）、搏动指数（PI）、阻力指数（RI），并比较 A 组与 B 组患者治疗 2、3、4 周血压达标率，母婴结局，治疗期间药物不良反应发生情况；入组次日血浆 Hcy 水平与 PIH 患者脐动脉血流动力学指标的相关性分析采用 Pearson 相关分析。结果　B 组 2 例患者因药物不良反应不能耐受而未按规定完成4 周治疗。A 组、B 组患者入组次日 SBP、DBP、血浆 Hcy 水平及脐动脉 S/D、PI、RI 高于对照组，脐动脉 VM 慢于对照组（P<0.01），而 A 组与 B 组患者入组次日 SBP、DBP、血浆 Hcy 水平及脐动脉 S/D、VM、PI、RI 比较，差异无统计学意义（P>0.05）；B 组患者治疗后 SBP、DBP、血浆 Hcy 水平及脐动脉 S/D、PI、RI 高于 A 组，脐动脉 VM 慢于 A 组（P<0.05）。Pearson 相关分析结果显示，入组次日血浆 Hcy 水平与 PIH 患者脐动脉 PI、RI、S/D 呈正相关（r值分别为 0.55、0.46、0.42，P<0.01），与脐动脉 VM 呈负相关（r=-0.38，P<0.01）。A 组与 B 组患者治疗 2、3、4周血压达标率比较，差异无统计学意义（P>0.05）。两组患者轻度子痫前期、胎盘早剥发生率比较，差异无统计学意义（P>0.05）；B 组患者中行剖宫产者所占比例高于 A 组，胎龄、新生儿出生体质量及 Apgar 评分低于 A 组（P<0.05）。B 组患者治疗期间药物不良反应发生率高于 A 组（P<0.05）。结论　PIH 患者血浆 Hcy 水平明显升高，脐动脉血流动力学指标异常；与硝苯地平片缓释片相比，拉贝洛尔片可更有效地降低 PIH 患者血压、血浆 Hcy 水平并改善脐动脉血流动力学指标、母婴结局，且安全性较高，应重视 PIH 患者降压药物的选择；血浆 Hcy 水平与 PIH 患者脐动脉血流动力学指标有关，PIH 患者可适当补充外源性叶酸；PIH 患者降压阈值定为≥ 150/100 mm Hg、降压目标值定为 130~140/80~90 mm Hg 可行，而基于无创血流动力学监测的 PIH 精准控压策略有助于最大限度地改善 PIH 患者母婴结局。

Abstract：

Background　Reasonable control of blood pressure can not effectively reduce the risk of preeclampsiain patients with pregnancy-induced hypertension（PIH），however reasonable control of blood pressure and simultaneouslyincreasing the umbilical artery blood flow to the utmost extent are directly related to maternal and child outcomes in patientswith PIH，thus it is of great practical significance to discuss the precise blood pressure control strategy for PIH. ObjectiveTo compare the impact on blood pressure，plasma homocysteine level and hemodynamics of umbilical artery between labetaloltablets and nifedipine sustained-release tablets in patients with PIH，to tentatively explore the precise blood pressure controlstrategy for PIH based on non-invasive hemodynamic monitoring. Methods　From June 2015 to March 2019，a total of 120patients with PIH were selected in the General Clinics of Women and Children's Hospital of Hubei Province and Xinzhou DistrictBranch of Wuhan Central Hospital，and they were divided into A group and B group according to completely randomized designgrouping method by using SPSS 16.0 statistical software，with 60 cases in each group；meanwhile 60 healthy pregnant womenadmitted to Women and Children's Hospital of Hubei Province for antenatal care and childbirth were selected as control group.Taking ≥ 150/100 mm Hg as the blood pressure threshold of initiating antihypertensive therapy and 130~140/80~90 mm Hg asblood pressure control up to standard，patients in A group received oral labetalol tablets，while patients in B group receivednifedipine sustained-release tablets；both groups continuously treated for 4 weeks. SBP，DBP，plasma Hcy level as well as S/D，VM，PI and RI of umbilical artery were compared in the three groups the day after grouping，between A group and B groupafter treatment；rate of blood pressure control up to standard 2，3，4 weeks after treatment，maternal and child outcomes andincidence of adverse reactions were compared between A group and B group；Pearson correlation analysis was used to analyzethe correlation between plasma Hcy level the day after grouping and hemodynamic index of umbilical artery in patients with PIH.Results　Two cases did not completed the 4-week treatment due to adverse drug reaction in B group. SBP，DBP，plasma Hcylevel as well as S/D，VM，PI and RI of umbilical artery in groups A and B were statistically significantly higher than those incontrol group the day after grouping（P<0.01），VM of umbilical artery in groups A and B was statistically significantly slowerthan that in control group，respectively（P<0.01），while no statistically significant difference of SBP，DBP，plasma Hcylevel，S/D，VM，PI or RI of umbilical artery was found between A group and B group（P>0.05）；SBP，DBP，plasmaHcy level as well as S/D，PI and RI of umbilical artery in B group were statistically significantly higher than those in A groupafter treatment，while VM in B group was statistically significantly slower than that in A group（P<0.05）. Pearson correlationanalysis results showed that，plasma Hcy level the day after grouping was positively correlated with PI（r=0.55），RI（r=0.46）and S/D（r=0.42）of umbilical artery in patients with PIH，respectively（P<0.01），but was negatively correlated with VMof umbilical artery（r=-0.38，P<0.01）. There was no statistically significant difference in rate of blood pressure control up tostandard between A group and B group 2，3，4 weeks after treatment（P>0.05）. No statistically significant difference of mildpreeclampsia or placental abruption was found between the two groups（P>0.05）；proportion of patients underwent cesareandelivery in B group was statistically significantly higher than that in A group，while gestational age，birth weight and Apgar scoreof the newborns in B group were statistically significantly lower than those in A group（P<0.05）. Incidence of adverse drugreaction in B group was statistically significantly higher than that in A group during treatment（P<0.05）. Conclusion　PlasmaHcy level significantly elevates and there is abnormity of hemodynamics of umbilical artery in patients with PIH；compare tonifedipine sustained-release tablets，labetalol tablets can more effectively reduce the blood pressure，plasma Hcy level as wellas improve the hemodynamics of umbilical artery，maternal and child outcomes in patients with PIH，with higher safety，thuswe should pay attention to the choice of antihypertensive drugs；plasma Hcy level is significantly correlated with hemodynamicindex of umbilical artery in patients with PIH，so it is for reference that patients with PIH may properly take exogenous folicacid；taking ≥150/100 mm Hg as the blood pressure threshold of initiating antihypertensive therapy and 130~140/80~90 mm Hgas blood pressure control up to standard are feasible in patients with PIH，however the precise blood pressure control strategy forPIH based on non-invasive hemodynamic monitoring is helpful to improve the maternal and child outcomes to the utmost extent.

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