摘要
目的:探讨慢性肾脏病(CKD)患者血清不对称性二甲基精氨酸(ADMA)水平及其与动脉粥样硬化(AS)的关系。方法:入选CKD患者138例(非透析治疗64例,血液透析74例)和年龄匹配的健康对照42例。高效液相色谱法(HPLC)检测血清L-精氨酸(L-Arg)、ADMA及对称性二甲基精氨酸(SDMA)水平,DTNB法测定全血硒谷胱甘肽过氧化物酶(SeGSHPx)活性,硫代巴比妥酸法测定血清丙二醛(MDA)水平;高分辨超声技术检测颈动脉内膜—中层厚度(IMT),切面内膜中层面积(cIMarea)、平均腔静脉内径及粥样硬化斑块。结果:CKD患者血清ADMA(1.77±0.32)μmol/L及SDMA水平(0.39±0.12)μmol/L明显高于正常对照组ADMA(0.51±0.15)μmol/L;SDMA(0.21±0.06)μmol/L,P<0.01。非透析CKD病人血清ADMA及SDMA水平与内生肌酐清除率(Ccr)呈负相关(r=-0.315,P=0.023;r=-0.426,P=0.001)。透析病人血清ADMA(2.04±1.39)μmol/L及SDMA水平(0.44±0.13)μmol/L明显高于非透析的CKD患者ADMA(1.28±0.89)μmol/L;SDMA(0.36±0.10)μmol/L,P<0.05。颈动脉有斑块的CKD患者血清ADMA(1.83±0.42)μmol/L)明显高于无斑块者(1.31±0.37)μmol/L。直线相关分析显示CKD患者血清ADMA水平与IMT(r=0.494,P=0.001)及cIMarea(r=0.318,P=0.001)呈正相关。经Ccr、年龄、性别及其他与AS相关因素校正后,多因素逐步回归分析结果显示血清ADMA与CRP是颈动脉内膜中层厚度(β=0.326,P<0.001)和切面内膜中层面积(β=0.296,P<0.05)的独立危险因素。结论:CKD患者血清ADMA及SDMA水平随肾功能减退而增高,ADMA与CKD患者动脉粥样硬化的发生关系密切并与氧化应激程度相关。
Objective To determine the association between asymmetric dimethylarginine （ADMA）, an endogenous inhibitor of nitric oxide （NO） synthase, with atherosclerosis in patients with chronic kidney disease （CKD）. Methods One hundred thirty-eight CKD patients were enrolled in this study. Serum levels of L-arginine, ADMA, and SDMA were measured by high-performance liquid chromatography （HPLC）. Common carotid arteries intimae-medial thickness （CCA-IMT） , cross-sectional calculated intimae-medial thickness （clM area）and atherosclerotic plaque were detected by noninvasive high-resolution B-mode ultrasonography. Results Serum levels of ADMA and SDMA were significantly increased in CKD patients （n = 138） compared with age matched healthy subjects （n =42,P 〈0.01 ）. ADMA and SDMA levels increased with the progression of renal dysfunction and were negatively related to creatinine clearance （Ccr） in pre-dialysis patients （r = -0. 315,P 〈 0.05;r = -0.426, P 〈 0.01 ）. Serum levels of ADMA and SDMA in dialysis patients （n = 74）were significantly higher than those in pre-dialysis patients （ P 〈 0.05 ）. Patients with carotid artery plaques showed significantly higher levels of ADMA compared with those without plaques. Serum levels of ADMA closely correlated with the mean IMT （r = 0.471, P 〈0.01 ） and cIM area value （r =0. 430, P 〈 0.01 ）. These correlations remained significant even after adjusting GFR,age, gender , and other risk factors for atherosclerosis in the multiple regression analysis. Conclusion Serum levels of ADMA increased with the progression of CKD and may play a role in the pathogenesis of accelerated atherosclerosis in CKD patients.
出处
《中南大学学报（医学版）》
CAS
CSCD
北大核心
2006年第5期621-628,共8页
Journal of Central South University ：Medical Science
基金
This work was supported by the National Nature and Sciences Grant (No. 30330300 andNo.30470806) and Committee of Provincial Science Study Foundation of Hunan (C2005-002)
