【摘要】目的探讨维持性血液透析(maintenance hemodialysis，MHD)患者血清骨硬化蛋白(sclerostin)水平与动脉僵硬度的关系及其影响因素。方法选择透析龄≥3 个月的MHD 患者110 例(MHD 组)和健康对照40 例为对象，ELISA 测定血清sclerostin 水平；检测肱踝脉搏波传导速度(brachial-ankle pulse wave velocity，baPWV)，采用直线相关与多元逐步Logistic 回归分析sclerostin 水平的影响因素及其与baPWV 的关系。结果MHD 组血清sclerostin 水平和baPWV 显著高于对照组(t 值分别为5.654，3.722；P 值分别为＜0.001，＜0.001)；Person 相关分析显示MHD 组sclerostin 水平与全段甲状旁腺激素(intact parathyroid hormone，iPTH)、血磷、超敏C 反应蛋白(high sensitive C-reactive protein, hsCRP)、平均动脉压(mean arterial pressure, MAP)呈正相关(r 值分别为0.397, 0.364, 0.536, 0.397；P 值分别为＜0.001，＜0.001，＜0.001，0.037)。多元逐步回归分析显示，hsCRP、血磷和iPTH 是影响sclerostin 的独立因素(ß 值分别为0.286, 0.218, 0.196；P 值分别为0.021, 0.027, 0.033)。根据baPWV 值将患者血管硬化程度分为正常、轻度硬化、中度硬化和重度硬化，结果显示动脉硬化(baPWV＞1400cm/s)患病率91.8%；各组间比较，重度硬化组患者血清sclerostin、hsCRP、MAP 及年龄较高(F 值分别为16.043，3.552，4.736，9.074；P 值分别为＜0.001，0.021，0.010，＜0.001)。Spearman相关分析显示，MHD 患者ba-PWV 与年龄、MAP、sclerostin、血磷、hs-CRP 呈正相关(r 值分别为0.368，0.397，0.571，0.224，0.278；P 值分别为＜0.001，＜0.001，＜0.001，0.035，0.008)。多因素Logistic 回归分析显示校正年龄、MAP 后，sclerostin 是影响ba-PWV 的独立危险因素(OR=1.292，95% CI 1.017～1.641，P=0.012)。结论MHD 患者动脉硬化发生率高，血清sclerostin 与动脉僵硬度可能相关。sclerostin升高是动脉硬化的独立危险因素。
【Abstract】Objective To investigate the serum sclerostin level and explore its relationship with brachialankle pulse wave velocity (baPWV) in maintenance hemodialysis (MHD) patients. Methods A total of 110 stable MHD patients undergoing hemodialysis for at least three months and 40 healthy individuals as the controls were enrolled in the study. Serum level of sclerostin was measured by ELISA and baPWV was determined. Their baseline characteristics and laboratory measurements were collected, and correlation analysis of sclerostin with baPWV and other parameters was performed. Results Serum sclerostin level and baPWV were significantly higher in MHD patients as compared with those in healthy controls (73.34±30.08 ng/L vs. 21.13±13.69 ng/L, t=5.654, P＜0.001 for serum sclerostin; 1875.96±375.38 cm/s vs. 1343.14±131.38 cm/s, t=3.722, P＜0.001 for baPWV). Sclerostin level was positively correlated with intact parathyroid hormone (iPTH) (r=0.397, P＜0.001), phosphorus (P) (r=0.364, P＜0.001), high sensitive c-reactive protein (hsCRP) (r=0.536, P＜0.001), and mean arterial pressure (MAP) (r=0.397, P=0.037). Multivariate stepwise regression showed that hsCRP (β=0.286, P=0.021), P (β=0.218, P=0.027) and iPTH (β=0.196, P=0.033) were the independent risk factors for sclerostin. Based on baPWV value, the degree of arterial sclerosis in MHD patients can be categorized into non-, slight, moderate and severe arteriosclerosis. The incidence of arteriosclerosis (baPWV ＞1400 cm/s) was 91.8% in this series of MHD patients. Sclerostin (F=16.043, P＜0.001), hsCRP (F=3.552, P=0.021), MAP (F=4.736, P=0.010) and age (F=9.074, P＜0.001) were significantly higher in baPWV ≥1800 m/s patients. In MHD patients, baPWV was positively correlated with age (r= 0.368, P＜0.001), MAP (r=0.397, P＜0.001), sclerostin (r=0.571, P＜0.001), P (r=0.224, P=0.035) and hs-CRP (r=0.278, P= 0.008). Multivariate stepwise regression showed that sclerostin level was still the independent risk factors for baPWV in MHD patients (OR=1.292, 95% CI=1.017～1.641, P=0.012) after adjusting age and MAP. Conclusion The incidence of arteriosclerosis is high in MHD patients. Serum sclerostin level may relate to arterial stiffness. Higher sclerostin level is the independent risk factors for arteriosclerosis.
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