红酒可预防同型半胱氨酸诱导的猪冠状动脉内皮功能障碍。

Red wine prevents homocysteine-induced endothelial dysfunction in porcine coronary arteries.

作者信息

Fu Weiping, Conklin Brian S, Lin Peter H, Lumsden Alan B, Yao Qizhi, Chen Changyi

机构信息

Molecular Surgeon Research Center, Michael E. DeDakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.

出版信息

J Surg Res. 2003 Nov;115(1):82-91. doi: 10.1016/s0022-4804(03)00247-6.

DOI:10.1016/s0022-4804(03)00247-6

PMID:14572777

Abstract

BACKGROUND

Hyperhomocysteinemia is an independent risk factor of coronary artery disease. Clinical studies have indicated that moderate red wine consumption is associated with a reduction of incidence of coronary artery disease. In this study, we determined the effect of red wine on homocysteine- induced endothelial dysfunction in porcine coronary arteries.

MATERIALS AND METHODS

Porcine coronary arteries were dissected from 6 pig hearts and cut into 5-mm ring segments, which were assigned into 4 groups (9 rings/group): blank control, homocysteine treated (50 muM), red wine treated (0.08% alcohol), and homocysteine plus red wine treated. The rings were cultured in cell culture medium with or without treatment for 24 h. Myograph analysis was performed with U46619 (10(-7) M) for contraction and cumulative bradykinin (10(-9) to 10(-5) M) for endothelium-dependent relaxation. The endothelial nitric oxide synthase (eNOS) levels were analyzed by RT-PCR, Western blot, and immunohistochemistry.

RESULTS

In response to 10(-5) M bradykinin, porcine coronary artery rings treated with homocysteine (50 muM) showed a significant reduction of endothelium-dependent vasorelaxation by 43% as compared to controls (P < 0.05). However, rings treated with red wine (0.08% alcohol) plus homocysteine showed no significant difference as compared to controls. Endothelium-dependent vasorelaxation was not different between control and red wine treated groups. Furthermore, eNOS mRNA density levels were significantly reduced by 36% in homocysteine treated group as compared to controls (P < 0.05). eNOS protein levels were also substantially reduced in the homocysteine-treated group. However, red wine treatment reversed the effect of homocysteine-induced eNOS downregulation.

CONCLUSIONS

Homocysteine significantly impaired endothelial functions including endothelium-dependent vasorelaxation and eNOS mRNA and protein levels in porcine coronary arteries; and red wine effectively prevented homocysteine-induced endothelial dysfunction. This study suggests that protecting coronary endothelial cells from homocysteine damage may be an important mechanism of red wine for preventing coronary artery disease.

摘要

背景

高同型半胱氨酸血症是冠状动脉疾病的一个独立危险因素。临床研究表明，适量饮用红酒与冠状动脉疾病发病率的降低有关。在本研究中，我们确定了红酒对同型半胱氨酸诱导的猪冠状动脉内皮功能障碍的影响。

材料与方法

从6个猪心脏中取出冠状动脉，切成5毫米的环段，分为4组（每组9个环）：空白对照组、同型半胱氨酸处理组（50μM）、红酒处理组（0.08%酒精）和同型半胱氨酸加红酒处理组。将环段在细胞培养基中培养，有无处理24小时。用U46619（10^(-7)M）进行收缩分析，用累积缓激肽（10^(-9)至10^(-5)M）进行内皮依赖性舒张分析。通过RT-PCR、蛋白质印迹法和免疫组织化学分析内皮型一氧化氮合酶（eNOS）水平。

结果

对于10^(-5)M缓激肽，同型半胱氨酸（50μM）处理的猪冠状动脉环与对照组相比，内皮依赖性血管舒张显著降低43%（P<0.05）。然而，红酒（0.08%酒精）加同型半胱氨酸处理的环段与对照组相比无显著差异。对照组和红酒处理组之间内皮依赖性血管舒张无差异。此外，与对照组相比，同型半胱氨酸处理组中eNOS mRNA密度水平显著降低36%（P<0.05）。同型半胱氨酸处理组中eNOS蛋白水平也大幅降低。然而，红酒处理逆转了同型半胱氨酸诱导的eNOS下调作用。