【摘要】目的探究维持性血液透析(maintenance hemodialysis，MHD)患者血清巨噬细胞迁移抑制因子(macrophage migration inhibitory factor，MIF)水平与血管钙化的关系。方法选取哈尔滨医科大学附属第一医院收治的98 例MHD 患者，分为钙化组(n=64)和非钙化组(n=34)，收集受试者临床基线资料；分析血清MIF 水平与腹主动脉钙化积分(abdominal aortic calcification score，AACS)、血清白细胞介素-6(interleukin-6，IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)水平相关性；影响MHD 患者发生血管钙化的因素；血清MIF、25-羟维生素D[25-hydroxyvitamin D，25(OH)D]、血钙、血磷、全段甲状旁腺素(intact parathyroid hormone, iPTH)水平对MHD 患者发生血管钙化的预测价值。结果与非钙化组比较，钙化组25(OH)D 水平降低(t=15.408,P＜0.001)，血钙、血磷、iPTH、血清MIF、IL- 6、TNF- α 水平均升高(t 值分别为12.098,13.384,24.570,7.255,9.694,15.567;P 值分别＜0.001, ＜0.001,＜0.001,＜0.001,＜0.001,＜0.001)。血清MIF 水平与IL-6、TNF-α、AACS 呈正相关(r 值分别为0.666,0.693,0.501; P 值分别为＜0.001,＜0.001,＜0.001)。血清MIF、25(OH)D、血钙、血磷、iPTH水平单独检测对MHD患者发生血管钙化预测的曲线下面积分别为0.841、0.698、0.709、0.665、0.716；联合检测的AUC 为0.919，诊断效能优于单一指标检测。结论血清MIF 水平升高与MHD 患者炎症状态及血管钙化有关，是影响MHD 血管钙化发生的独立危险因素，与25(OH)D、血钙、血磷、iPTH 水平联合检测可能对MHD发生血管钙化有一定预测价值。
【Abstract】Objective T o investigate the relationship between serum macrophage migration inhibitory factor (MIF) level and vascular calcification in maintenance hemodialysis (MHD) patients. Methods A total of 98 MHD patients admitted to the First Hospital Affiliated to Harbin Medical University were recruited. They were divided into calcification group (n=64) and non-calcification group (n=34). Their baseline clinical data were collected. The correlations between serum MIF level and abdominal aortic calcification score (AACS), serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels were analyzed. We also analyzed the influencing factors for vascular calcification, and the predictive values of serum MIF, 25-hydroxyvitaminD (25(OH)D), calcium, phosphorus and intact parathyroid hormone (iPTH) levels for vascular calcification in MHD patients. Results In calcification group, serum 25(OH)D level decreased significantly (t=15.408, P<0.001), while serum calcium, phosphorus, iPTH, MIF, IL- 6 and TNF-α levels increased (t=12.098, 13.384, 24.570, 7.255, 9.694 and 15.567 respectively; P＜0.001) as compared with those in non-calcification group. Serum MIF level was positively correlated with IL- 6 and TNF- α levels and AACS score (r=0.666, 0.693,
0.501; P<0.001). The areas under curves (AUCs) of serum MIF, 25(OH)D, calcium, phosphorus and iPTH for the diagnosis of vascular calcification in MHD patients were 0.841, 0.698, 0.709, 0.665 and 0.716 respectively; the AUC of integrated serum biochemical parameters was 0.919, better than the diagnostic efficiency using single serum biochemical parameter. Conclusions Serum MIF level increased significantly in MHD patients,which is related to the inflammatory state and vascular calcification, and is an independent risk factor for vascular calcification in MHD patients. Integrated estimation of serum MIF, 25(OH)D, calcium, phosphorus and iPTH levels will be more useful for the prediction of vascular calcification in MHD patients.
[1] Kaihan AB, Hishida M, Imaizumi T, et al. Circulating levels of CD34+ cells predict long-term cardiovascular outcomes in patients on maintenance hemodialysis[J]. PLoS One,2019,14(10):223390-223402.
[2] 刘芳婕，徐天华，姚丽. 维持性血液透析患者中血清同型半胱氨酸与心血管疾病相关性研究[J]. 中国实用内科杂志,2018,38(6):559-561.
[3] Mizuiri S, Nishizawa Y, Yamashita K, et al. Relationship of matrix Gla protein and vitamin K with vascular calcification in hemodialysis patients[J]. Ren Fail,2019,41(1):770-777.
[4] 董谦谦，颜建云. 血管钙化参与细胞相关研究的新进展[J]. 中国动脉硬化杂志,2018,26(11):1111-1115.
[5] Zhao Q, Men L, Li XM, et al. Circulating MIF levels predict clinical outcomes in patients with st-elevation myocardial infarction after percutaneous coronary intervention[J]. Can J Cardiol,2019,35(10):1366-1376.
[6] Bilsborrow JB, Doherty E, Tilstam PV, et al. Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus[J]. Expert Opin Ther Targets,2019,23(9):733-744.
[7] Bae SH, Yoo MR, Kim YY, et al. Brain-derived neurotrophic factor mediates macrophage migration inhibitory factor to protect neurons against oxygen-glucose deprivation[J]. Neural Regen Res,2020,15(8):1483-1489.
[8] 杨菁，朱悦倩，赵洪婷，等. 巨噬细胞迁移抑制因子在中枢神经系统中的作用研究进展[J].中华神经医学杂志,2019, 18(9):952-956.
[9] Sinitski D, Kontos C, Krammer C, et al. Macrophage Migration Inhibitory Factor (MIF)-Based Therapeutic Concepts in Atherosclerosis and Inflammation[J]. Thromb Haemost,2019,119(4):553-566.
[10] Chen HC, Wang WT, Hsi CN, et al. Abdominal aortic calcification score can predict future coronary artery disease in hemodialysis patients: a 5-year prospective cohort study[J]. BMC Nephrol,2018,19(1):313-319.
[11] Ryoo HG, Paeng JC, Koo BK, et al. Clinical implication of 18F-NaF PET/computed tomography indexes of aortic calcification in coronary artery disease patients: correlations with cardiovascular risk factors[J]. Nucl Med Commun,2020,41(1):58-64.
[12] 江杰，郑东文，李仪，等. 维持性血液透析患者冠状动脉钙化相关危险因素分析[J].中国血液净化,2018,17(6):388-390.
[13]Zhao W, Wang Y, Kong W, et al. Elevated serum cartilage oligomeric matrix protein and the metalloproteinase‐ADAMTS7 levels are associated with vascular calcification in maintenance hemodialysis patients[J]. Semin Dial,2020,33(4):322-329.
[14] 贺晓雯, 徐玉祥, 张九芝, 等. 行维持性血液透析治疗的患者血清骨桥蛋白、血管内皮生长因子、基质金属蛋白酶9水平及其与血管钙化的关系[J].广西医学,2020,42(8):934-937.
[15] 李大勇，袁新科，刘冠兰，等. 维持性血液透析患者血清Irisin、BMP-7水平与血管钙化及钙磷代谢指标的相关性研究[J]. 中国现代医学杂志,2019,29(15):41-46.
[16] 韩建芳, 李丽华, 王宁宁, 等. 维持性血液透析患者慢性肾脏病矿物质和骨异常患病情况调查及血管钙化的危险因素分析[J].现代生物医学进展,2020,20(5):953-956+965.
[17] Kara AV, Soylu YE. The relationship between vitamin D and inflammatory markers in maintenance hemodialysis patients[J]. Int Urol Nephrol,2019,51(9):1659-1665.
[18] 蓝天座，于黔，樊丰夷，等. 维持性血液透析患者血清cTnT、CRP、IL-6、TNF-α水平与预后的关系[J]. 山东医药,2017,57(38):84-86.
[19] Henaut L, Candellier A, Boudot C, et al. New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease[J]. Toxins (Basel),2019,11(9):529-561.
