雌激素可阻止同型半胱氨酸诱导的猪冠状动脉内皮功能障碍(1,2)。

Estrogen blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries(1,2).

作者信息

Spencer Todd A, Chai Hong, Fu Weiping, Ramaswami Ganesh, Cox Mitchell W, Conklin Brian S, Lin Peter H, Lumsden Alan B, Yao Qizhi, Chen Changyi

机构信息

Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine and the Methodist Hospital, Houston, Texas 77030, USA.

出版信息

J Surg Res. 2004 May 1;118(1):83-90. doi: 10.1016/j.jss.2004.01.021.

DOI:10.1016/j.jss.2004.01.021

PMID:15093721

Abstract

BACKGROUND

The objective of this study was to examine the effect of estrogen combined with homocysteine on vasomotor function and endothelial integrity in intact porcine coronary arteries.

MATERIALS AND METHODS

Pig coronary artery rings were incubated with estrogen, homocysteine, or estrogen and homocysteine for 24 h. Myographic analysis was performed with thromboxane A2 analog U46619 for contraction and bradykinin or sodium nitroprusside for relaxation. Endothelial nitric oxide synthase (eNOS) levels were determined by immunohistochemistry. Levels of superoxide anion were assessed by lucigenin-enhanced chemiluminescence analysis.

RESULTS

Endothelium-dependent vasorelaxation (bradykinin) for the homocysteine alone group was 62% compared with control (P < 0.05), and endothelium-dependent vasorelaxation for the estrogen alone group was 85% compared with control (P > 0.05). Endothelium-dependent vasorelaxation for the estrogen-homocysteine combined group was 79% compared with 89% for control (P > 0.05). There were no differences in endothelium-independent vasorelaxation (sodium nitroprusside) or in smooth muscle contractility (U46619) between all three groups and control. In addition, the eNOS immunoreactivity was declined in the homocysteine group and had no major change in the estrogen or estrogen plus homocysteine-treated group as compared with controls. The superoxide free radical measurement showed a marked increase in the homocysteine group, no major change from controls in the estrogen group, and a much-lessened effect in the combination of estrogen and homocysteine.

CONCLUSIONS

These data demonstrate that combining estrogen with homocysteine significantly blocks the effect of homocysteine on impairing endothelium-dependent vasorelaxation as well as on decreasing eNOS expression and increasing oxidative stress in porcine coronary arteries. This study suggests that estrogen may play a role in preventing homocysteine-mediated endothelial dysfunction and may be of benefit in the hyperhomocysteinemic patient.

摘要

背景

本研究的目的是检测雌激素联合同型半胱氨酸对完整猪冠状动脉血管舒缩功能和内皮完整性的影响。

材料与方法

将猪冠状动脉环分别与雌激素、同型半胱氨酸或雌激素与同型半胱氨酸一起孵育24小时。采用血栓素A2类似物U46619进行收缩实验，用缓激肽或硝普钠进行舒张实验，进行肌动描记分析。通过免疫组织化学法测定内皮型一氧化氮合酶（eNOS）水平。通过光泽精增强化学发光分析法评估超氧阴离子水平。

结果

单独同型半胱氨酸组的内皮依赖性血管舒张（缓激肽）为62%，与对照组相比（P < 0.05）；单独雌激素组的内皮依赖性血管舒张为85%，与对照组相比（P > 0.05）。雌激素 - 同型半胱氨酸联合组的内皮依赖性血管舒张为79%，对照组为89%（P > 0.05）。三组与对照组之间在内皮非依赖性血管舒张（硝普钠）或平滑肌收缩性（U46619）方面没有差异。此外，与对照组相比，同型半胱氨酸组的eNOS免疫反应性下降，雌激素组或雌激素加同型半胱氨酸处理组没有重大变化。超氧自由基测量显示同型半胱氨酸组显著增加，雌激素组与对照组相比没有重大变化，雌激素和同型半胱氨酸联合组的影响大大减轻。