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慢性肾脏病患者的血管性血友病因子、ADAMTS13活性、肿瘤坏死因子-α及其相互关系

Von Willebrand factor, ADAMTS13 activity, TNF-α and their relationships in patients with chronic kidney disease.

作者信息

Shen Lei, Lu Guoyuan, Dong Ningzheng, Jiang Liqiong, Ma Zhenni, Ruan Changgeng

机构信息

Department of Nephrology, The First Affiliated Hospital of Soochow University;

出版信息

Exp Ther Med. 2012 Mar;3(3):530-534. doi: 10.3892/etm.2011.432. Epub 2011 Dec 23.

DOI:10.3892/etm.2011.432
PMID:22969924
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3438530/
Abstract

Patients with chronic kidney disease (CKD) often exhibit associated endothelial dysfunction and inflammation. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. In this study, we assessed the relationships among endothelial dysfunction, a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) activity and levels of inflammatory cytokines in CKD patients. CKD patients were classified into three groups: The chronic glomerulonephritis group (CGN; n=31), the idiopathic nephritic syndrome group (NS; n=32) and the lupus nephritis group (LN; n=41). We measured the plasma levels of tumor necrosis factor-α (TNF-α), von Willebrand factor (VWF) antigen (VWF:Ag) and ADAMTS13 activity using an ELISA-based method in CKD patients (n=104) and normal controls (n=32). The ratio of the VWF:Ag levels to ADAMTS13 activity was calculated. The VWF:Ag levels were significantly higher and the ADAMTS13 activities were significantly lower in the disease groups compared to the controls (P<0.01). ADAMTS13 activity was lower in the NS group compared to the CGN and LN groups (P<0.05). The TNF-α levels were higher in the CKD group compared to the control group (P<0.01). TNF-α was positively correlated with the VWF:Ag levels (r=0.242, P=0.013) and negatively correlated with the glomerular filtration rate (GFR) (r=-0.193, P=0.049). ADAMTS13 activity was negatively correlated with the cholesterol levels in CKD patients (r=-0.2, P= 0.042). TNF-α levels in CKD were positively correlated with the VWF:Ag levels and negatively correlated with GFR, which indicates that inflammation may be a major cause of endothelial dysfunction and an index of renal function. The VWF:Ag levels increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state.

摘要

慢性肾脏病(CKD)患者常伴有内皮功能障碍和炎症。全身炎症可能导致CKD患者出现内皮功能障碍和血栓形成加速。在本研究中,我们评估了CKD患者内皮功能障碍、具有血小板反应蛋白基序的解聚素样金属蛋白酶13(ADAMTS13)活性与炎症细胞因子水平之间的关系。CKD患者被分为三组:慢性肾小球肾炎组(CGN;n = 31)、特发性肾病综合征组(NS;n = 32)和狼疮性肾炎组(LN;n = 41)。我们采用基于酶联免疫吸附测定(ELISA)的方法,检测了104例CKD患者和32例正常对照者血浆中肿瘤坏死因子-α(TNF-α)、血管性血友病因子(VWF)抗原(VWF:Ag)水平以及ADAMTS13活性。计算VWF:Ag水平与ADAMTS13活性的比值。与对照组相比,疾病组的VWF:Ag水平显著升高,ADAMTS13活性显著降低(P < 0.01)。与CGN组和LN组相比,NS组的ADAMTS13活性较低(P < 0.05)。与对照组相比,CKD组的TNF-α水平较高(P < 0.01)。TNF-α与VWF:Ag水平呈正相关(r = 0.242,P = 0.013),与肾小球滤过率(GFR)呈负相关(r = -0.193,P = 0.049)。CKD患者中,ADAMTS13活性与胆固醇水平呈负相关(r = -0.2,P = 0.042)。CKD患者的TNF-α水平与VWF:Ag水平呈正相关,与GFR呈负相关,这表明炎症可能是内皮功能障碍的主要原因及肾功能指标。CKD患者的VWF:Ag水平升高,ADAMTS13活性降低,这表明CKD导致了血栓前状态。

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