Attenuation of oxidative stress and hypertension in an animal model of HELLP syndrome.
Attenuation of oxidative stress and hypertension in an animal model of HELLP syndrome.
复制标题
HELLP 综合征动物模型中氧化应激和高血压的减弱。
DOI：
10.1016/j.ejphar.2018.07.013
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发表时间：
2018
影响因子：
5
通讯作者：
Wallace,Kedra
中科院分区：
文献类型：
--
作者：
Morris,Rachael;Spencer,Shauna-Kay;Barnes,Allison;Bowles,Teylor;Kyle,PatrickB;Wallace,Kedra
HELLP（溶血升高肝酶低血小板）综合征与高血压、炎症、氧化应激和内皮活化有关。本研究的目的是确定清除氧或内皮素A受体拮抗剂是否能改善高血压和氧化应激。将sFlt-1和sEndoglin于妊娠第12天通过微渗透泵注入正常妊娠大鼠体内，形成HELLP综合征。在妊娠第19天插入18根动脉导管，分析妊娠第19天大鼠平均动脉压；采集血清、尿液和组织进行分子分析。与正常妊娠大鼠相比，help大鼠的MAP明显升高（P < 0.0005）。通过ABT-627和Tempol（模拟超氧化物歧化酶）对正常妊娠大鼠和HELLP大鼠进行内皮素A受体拮抗剂治疗，从妊娠第13天开始，HELLP大鼠的平均动脉压降低（P < 0.05;P < 0.005）。NP+ETAReceptor或NP+Tempol治疗大鼠与NP大鼠平均动脉压差异无统计学意义（P = 0.22）。内皮素A受体阻断显著降低HELLP诱导的异前列腺素排泄（P < 0.0005）、胎盘和肝脏活性氧（P < 0.05;P < 0.0005）和胎盘总抗氧化能力（P < 0.005）。在异前列腺素（P < 0.005）、肝脏活性氧（P < 0.05）和胎盘总抗氧化能力（P < 0.05）方面，使用Tempol或内皮素A受体拮抗剂治疗的HELLP大鼠与未治疗的HELLP大鼠的结果相似。这些数据证明了氧化应激在高血压、胎盘和肝脏损伤中所起的作用，这些在HELLP综合征中可见。
HELLP (hemolysis elevated liver enzyme low platelet) syndrome is associated with hypertension, inflammation, oxidative stress and endothelial activation. The objective of this study was to determine if oxygen scavenging or endothelin A receptor antagonism improved hypertension and oxidative stress. sFlt-1 and sEndoglin were infused via mini-osmotic pump into normal pregnant rats (NP) on gestational day 12 to create HELLP syndrome. On gestational day 18 arterial catheters were inserted and on gestational day 19 mean arterial pressure was analyzed in rats; serum, urine and tissues were collected for molecular analysis. HELLP rats had significantly increased MAP compared to control normal pregnant rats (P < 0.0005). Endothelin A receptor antagonism via ABT-627 and Tempol, superoxide dismutase mimetic, were administered to a subset of normal pregnant and HELLP rats beginning on gestational day 13 and attenuated mean arterial pressure in HELLP rats (P < 0.05; P < 0.005). There were no statistically significant differences in mean arterial pressure between NP+ETAReceptor or NP+Tempol treated rats and NP rats (P = 0.22). Endothelin A receptor blockade significantly decreased HELLP induced isoprostane excretion (P < 0.0005), placental and hepatic reactive oxygen species (P < 0.05; P < 0.0005) and increased placental total antioxidant capacity (P < 0.005) compared to untreated HELLP rats. Similar results in isoprostane (P < 0.005), hepatic reactive oxygen species (P < 0.05) and placental total antioxidant capacity (P < 0.05) were seen in HELLP rats treated with Tempol or Endothelin A receptor antagonist vs. untreated HELLP rats. These data demonstrated a role for oxidative stress in contributing to the hypertension, placental and liver damage that is seen in HELLP syndrome.