人颈动脉粥样硬化斑块组织及外周血白细胞相对端粒长度的检测及相关性分析

目的研究人颈动脉粥样硬化斑块组织与外周血白细胞的DNA相对端粒长度是否有相关性，外周血白细胞能否反映血管组织的相对端粒长度，从而为外周血白细胞端粒长度与动脉粥样硬化的相关性研究提供依据。方法分别取12例颈动脉内膜剥脱术患者的颈动脉内膜斑块组织及外周血，提取DNA，采用实时荧光定量PCR（qRT-PCR）的方法检测相对端粒长度，并进行相关性分析。结果人颈动脉斑块的平均相对端粒长度（Relativetelomerelength，RTL）为0.56士0.12（平均值士标准差），显著高于外周血白细胞的平均相对端粒长度（0.45±0．13）（P=0.038）。多元线性回归方法校正年龄、性别、体重指数、血脂水平、高血压、糖尿病等心血管病危险因素，表明来自同一患者颈动脉斑块组织和外周血白细胞的RTL具有显著的相关性（标化相关系数β=0.87；P=-0.0001）；外周血白细胞RTL与年龄呈负相关（标化相关系数β=0.704，P〈0.001）；颈动脉斑块样本RTL与年龄呈负相关（标化相关系数β=-0.528，P=0.002）。结论人颈动脉斑块组织与外周血白细胞的相对端粒长度具有相关性，外周血白细胞是替代血管组织研究端粒长度与心血管疾病关系的一个重要指标。

Comparison of blood leukocyte telomere DNA content and vascular telomere DNA content in human carotid atherosclerotic plaques

Objective To investigate the relationship of relative telomere lengths (RTL) of vascular wall and circulating leukocytes in atherosclerosis patients with carotid endarterectomy.Methods Carotid atherosclerotic plaques and paired blood leukocytes were obtained from 12 patients with atherosclerosis,and relative telomere lengths were measured by real-time quantitative PCR (qRT-PCR).The correlation between the RTLs of two tissues was assessed.Results The average RTL of carotid atherosclerotic plaques (mean ± SD,0.56 ± 0.12) was significantly higher than that of blood leukocytes (0.45 ± 0.13) (P=0.038).Multivariable linear regression analysis showed a positive association between the telomere lengths in pairs of leukocytes and carotid plaque specimens from the same subject (Standardized coefficient β=0.87;P=0.0001).The telomere length was inversely correlated with age in blood leukocytes (Standardized coefficient β=-0.704,P<0.001) and in atherosclerotic plaque specimens (Standardized coefficient β=-0.528,P=0.002).Conclusion Our findings demonstrate that the leukocyte DNA content is a predictor of telomere content of vascular tissue and is an appropriate surrogate for human vascular age.