非对性性二甲基精氨酸及循环内皮祖细胞与冠状动脉病变程度的相关性
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湖南省科技厅项目(2013SK3193)


The Relationship Between Asymmetric Dimethylarginine as well as Circulating Endothelial Progenitor Cells and the Severity of Coronary Lesions in Patients with Coronary Heart Disease
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    摘要:

    目的 探讨冠心病患者非对称性二甲基精氨酸(ADMA)及循环内皮祖细胞(EPC)与冠状动脉病变程度的相关性。方法 80例冠心病患者均经选择性冠状动脉造影证实有明显的冠状动脉狭窄;50例对照者经选择性冠状动脉造影排除冠状动脉狭窄。根据病变程度分组,测定各组患者血浆ADMA水平;采集研究对象外周血进行EPC的分离培养;7~10天后倒置相差显微镜下计数细胞克隆形成单位(CFU)评估循环EPC数量。结果 冠心病单支及多支病变组血浆ADMA水平明显高于对照组(P<0.05和P<0.01),且多支病变组较单支病变组ADMA水平增高(P<0.05);冠状动脉病变Gensini积分≥60分组、31~59分组和≤30分组血浆ADMA水平均明显高于对照组;随着Gensini积分及病变支数的增加,血浆ADMA水平明显上升(P<0.05和P<0.01)。冠心病组中单支及多支病变组循环EPC数量明显低于对照组(P<0.05和P<0.01);冠状动脉病变Gensini积分三个分组中循环EPC数量明显低于对照组(P<0.01)。随着Gensini积分及病变支数的增加,EPC数量明显下降(P<0.05和P<0.01)。冠状动脉病变Gensini积分与血浆ADMA水平呈正相关(r0.365,P0.027),与循环EPC数量呈负相关(r-0.16,P0.015);血浆ADMA水平与循环EPC数量呈负相关(P<0.01)。结论 随着冠状动脉病变程度的增加,体内ADMA水平逐渐增加,而EPC数量逐渐减少,冠心病的发生与ADMA的蓄积及EPC的减少相关。体内实验进一步证实ADMA可能通过抑制EPC的功能影响内皮再生化。

    Abstract:

    Aim To investigate the relationship between the severity of coronary lesions and asymmetric dimethylarginine (ADMA) as well as circulating endothelial progenitor cells (EPC) in patients with coronary heart disease (CHD). Methods 130 cases were divided into two groups: CHD group(n80) and control group (n50), and CHD patients were divided into three groups according to the result of coronary angiography and the CHD Gensini’s scoring system. The levels of plasma ADMA were measured. Total mononuclear cell were isolated from peripheral blood by Ficoll density gradient centrifugation, and were cultured in medium supplemented with 10% fetal bovine serum, vascular endothelial growth faactor (VEGF) and basic fibroblast growth factor (bFGF). After 7~10 days cultured, the numbers of colony-forming units (CFU) of EPC were counted by phase-contrast microscope. Results The levels of plasma ADMA were significantly higher in single vessel disease group and multitude vessels disease group than those in control group (P<0.05 and P<0.01), and in Gensini’s scores ≥60 group, ADMA levels were significantly higher than those in control group (P<0.01). With the increase of Gensini’s scores and lesion count, plasma ADMA levels increased obviously (P<0.05 and P<0.01). Meanwhile, the numbers of CFU of circulating EPC were significantly lower in single vessel disease group and multitude vessels disease group than those in control group (P<0.01), and in Gensini’s scores ≥60 group, Gensini’s scores 31~59 group, Gensini’s scores ≤30 group, the circulating EPC numbers were significantly lower than that of control group (P<0.01). With the increase of Gensini’s scores and lesion count, EPC numbers decreased obviously(P<0.05 and P<0.01). The Gensini’s score of coronary lesion and plasma ADMA was positively correlated (r0.365, P0.027), and negatively correlated with the numbers of circulating EPC (r-0.16, P0.015). There was a strong negative correlation between the levels of plasma ADMA and the numbers of CFU of circulating EPC (P<0.01). Conclusions Corresponding with the degree of coronary atherosclerosis severer, the plasma CFU levels were higher in CHD group than those of control group, the numbers of circulating EPC of CHD patients were lower than those of healthy person. ADMA accumulation may contribute to EPC depletion, with consequent impairment of EPC-mediated endothelial repair, which can promote atherogenesis. ADMA was negatively correlated with the number of CFU of circulating EPC. In vivo ADMA can promote endothelial dysfunction by means of depressant EPC proliferation.

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何 晋,郑昭芬,郭 莹,彭建强,潘宏伟.非对性性二甲基精氨酸及循环内皮祖细胞与冠状动脉病变程度的相关性[J].中国动脉硬化杂志,2014,22(11):1127~1131.

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  • 收稿日期:2014-05-12
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