【摘要】目的观察尿毒症患者血管钙化(vascular calcification,VC)与骨硬化蛋白(Sclerostin)水平之间的相关性。方法采用ELISA 方法检测56 例行动静脉内瘘(arteriovenous fistula,AVF)成形术患者、56 例行维持性血液透析(maintenance hemodialysis,MHD)治疗患者和56 例健康人群的血清Sclerostin 水平；收集研究对象基本资料及生化指标；腹部CT 评估腹主动脉钙化发生情况；苏木精-伊红
(hematoxylin-eosin,HE)染色及茜素红染色观察桡动脉钙化情况。结果3 组对比发现AVF 组及MHD组患者的VC 发生率(F =29.973，P＜0.001)、磷(F =45.308,P＜0.001)、镁(F =42.468,P＜0.001)、尿酸(F=16.049,P＜0.001)、碱性磷酸酶(F=5.677,P= 0.005)、三酰甘油(F=5.521，P=0.005)、全段甲状旁腺激素(F=22.001，P＜0.001)、Sclerostin(F=202.458，P＜0.001)水平高于对照组；钙(F =15.006，P＜0.001)、25 羟维生素D 水平(F=9.904，P＜0.001)低于对照组。AVF 组内桡动脉钙化组患者年龄(t= 2.033，P =0.048)、磷(t=4.170，P＜0.001)、全段甲状旁腺激素(t=- 2.374，P =0.018)、Sclerostin(t=9.709，P＜0.001) 水平高于非钙化组。MHD 组中腹主动脉钙化组年龄(t=2.033, P=0.048)、磷(t=2.360, P =0.023)、碱性磷酸酶(t=2.122，P=0.040)、全段甲状旁腺激素(t=2.130，P =0.039)、Sclerostin(t=2.671，P =0.011)水平高于非钙化组。受试者特征工作曲线(receiver operating curve, ROC)分析，血清Sclerostin 预测AVF 组及MHD 组患者VC 的曲线下面积分别为0.895(95%CI 为0.815～0.976，P＜0.001，最佳截断值为5.55ng/ml，灵敏度为82.4%，特异度为86.4%)、0.746(95% CI 为0.593～0.898，P=0.007，最佳截断值为6.8555ng/ml，灵敏度为71.4%，特异度为81.2%)。结论VC 与年龄、磷、全段甲状旁腺激素、血清Sclerostin水平呈正相关。
【Abstract】Objective To observe the correlation between vascular calcification (VC) and serum sclerostin level in uremia patients. Method Serum sclerostin levels were detected by ELISA in 56 patients who underwent arteriovenous fistula operation (AVF group), 56 maintenance hemodialysis patients (MHD group), and 56 normal individuals (control group). Their demographic data and biochemical indicators were collected. Abdominal CT was used to evaluate abdominal aortic calcification. Hematoxylin-eosin (HE) staining and alizarin red staining were used to examine the calcification of the radial artery in surgical samples. Result VC rate (F=29.973, P＜0.001), serum phosphorus (F=45.308, P＜0.001), magnesium (F=42.468, P＜0.001),
uric acid (F=16.049, P＜0.001), alkaline phosphatase (F=5.677, P=0.005), triglyceride (F=5.521, P=0.005),immunoreactive parathyroid hormone(F=22.001, P＜0.001) and serum sclerostin(F=202.458, P＜0.001) were significantly higher in AVF and MHD groups than in control group. Serum calcium(F=15.006,P＜0.001) and 25-OH-vitamin D (F=9.904, P=0.000) were lower in AVF and MHD groups than in control group. In AVF group, patients with radial artery calcification had older age (t=2.033, P=0.048), and higher serum phosphorus (t=4.170,P＜0.001), immunoreactive parathyroid hormone (t=-2.374, P=0.018) and serum sclerostin (t=9.709, P＜0.001) than those without radial artery calcification. In MHD group, patients with abdominal aortic calcification had older age (t=2.033, P=0.048), and higher levels of phosphorus (t=2.360, P=0.023), alkaline phosphatase (t=2.122, P=0.040), immunoreactive parathyroid hormone (t=2.130, P=0.039) and serum sclerostin (t=2.671, P=0.011) than those without abdominal aortic calcification. ROC curve analysis showed that the area under the curve of serum sclerostin for prediction of VC in AVF group was 0.895 (95% CI 0.815~0.976, P＜0.001); at the optimal cut-off value of serum sclerostin 5.55ng/ml, the sensitivity of for the diagnosis of VC was 82.4%, the specificity was 86.4%. The area under the curve of serum sclerostin for prediction of abdominal aortic calcification in MHD group was 0.746 (95% CI 0.593~0.898, P=0.007); at the optimal cut-off value of 6.8555ng/ml, the sensitivity for the diagnosis of abdominal aortic calcification was 71.4% and the specificity was 81.2%. Conclusion VC was positively correlated with age, serum phosphorus, immunoreactive parathyroid hormone and serum sclerostin.
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