慢性肾病患者循环血小板微颗粒、内皮细胞微颗粒水平的变化
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摘要
目的比较慢性肾脏疾病(CKD)患者与正常对照组血浆中血小板微颗粒(PMPs)、血小板α-颗粒膜蛋白(GMP140)、内皮细胞微颗粒(EMPs)、血管性血友病因子(vWF)水平的变化,探讨PMPs、EMPs在慢性肾病中的意义。
方法收集苏州大学附属第一医院肾内科2007年2月至2008年6月住院的慢性肾病患者72例(定义和分期依据K/DOQI慢性肾脏病临床实践指南),健康正常对照组20例。采用流式细胞术检测血浆中PMPs、EMPs的水平;采用酶联免疫吸附试验(ELISA法)检测血浆中GMP140、vWF的水平;检测血压、身高、体重、用Cockcroft-Gault公式法计算肌酐清除率(Ccr(ml/min)=[(140-年龄)×体重×(0.85女性)]/(72×Scr));抽取空腹静脉血检测血红蛋白含量、血肌酐、血胆固醇、血糖;放射免疫法检测微量尿蛋白。
结果
1与对照组比较,慢性肾病组患者血浆PMPs及GMP140的水平均显著升高(P<0.05)。
2慢性肾病患者不同临床分类组之间血浆PMPs、GMP140的水平:肾病综合征组及慢性肾炎组患者血浆PMPs的含量均显著高于对照组(P<0.01,P<0.05),其中肾病综合征组血浆PMPs的含量显著高于高血压肾病组(P<0.05),其余各组间无显著性差异(P>0.05);各临床分类组患者血浆GMP140的含量均显著高于对照组(P<0.01),其中肾病综合征组血浆GMP140的含量显著高于狼疮性肾病组、糖尿病肾病组和高血压肾病组(P<0.01,P<0.05),慢性肾炎组血浆GMP140的含量显著高于糖尿病肾病组(P<0.01)。
3慢性肾病患者不同分期之间血浆PMPs、GMP140水平的比较:I期患者血浆中PMPs含量显著高于IV期(P<0.05),其余各组间无显著性差异(P>0.05);不同的CKD分期间GMP140含量无明显差异(P>0.05)。
4经相关性分析,慢性肾病患者血浆PMPs的水平与血压呈正相关(r=0.39,P <0.05),与肌酐清除率(r=-0.15,P>0.05)、24小时尿蛋白定量(r=0.18,P>0.05)、血红蛋白(r=-0.21,P>0.05)、血胆固醇(r=0.10,P>0.05)的相关性无显著性意义。GMP140的水平与PMPs呈正相关(r=0.31,P<0.05)。
5与对照组比较,慢性肾病组患者血浆EMPs及vWF的水平均显著升高(P<0.01)。
6不同临床类型的CKD患者血浆EMPs及vWF的含量均显著高于对照组(P<0.01,P<0.05),其中肾病综合征组血浆EMPs的含量显著高于高血压肾病组(P <0.05),其余各组间无显著性差异(P>0.05)。肾病综合征组血浆vWF的含量显著高于高血压肾病组及慢性肾炎组,其余各组间无显著性差异(P>0.05)。
7慢性肾病患者不同分期之间血浆EMPs、vWF水平的比较:I期患者血浆中EMPs含量显著高于IV期(P<0.05),其余各组间无显著性差异(P>0.05);不同的CKD分期间vWF含量无明显差异(P>0.05)。
8经相关性分析,vWF的水平与EMPs呈正相关(r=0.41,P<0.05),慢性肾病患者血浆EMPs的水平与血压呈正相关(r=0.52,P<0.01),与肌酐清除率(r=-0.12,P>0.05)、24小时尿蛋白定量(r=0.15,P>0.05)、血红蛋白(r=-0.22,P>0.05)、血胆固醇(r=0.07,P>0.05)的相关性无显著性意义。
结论
1慢性肾病患者存在明显的血小板活化及内皮功能障碍,血小板活化及内皮功能紊乱参与慢性肾病发生发展的病理生理过程。
2高血压是使慢性肾病患者血小板活化及内皮功能异常的重要原因之一。
3 PMPs、EMPs可作为一种反映血小板活化及内皮功能损伤的新标记。
Objective Compare the levels of PMPs、GMP140、EMPs and vWF in patients with chronic kidney disease and in normal control group, to explore the significance of the PMPs and EMPs in chronic kidney disease.
Methods From February 2007 to June 2008, 72 cases of patients with chronic kidney disease who were hospitalized in the First Affiliated Hospital of Suzhou University were enrolled in this study (Definition and phases were based on K / DOQI chronic kidney disease clinical practice guidelines) ,20 cases of healthy controls were also enrolled. Circulating PMPs and EMPs were numerated by flow cytometry;GMP140 and vWF were measured by the enzyme-linked immunosorbent assay; The blood pressure, height and weight of all subjects were measured also.The Cockcroft-Gault formula to calculate creatinine clearance (Ccr (ml / min) = [(140 - age)×weight×(0.85 for women)] / (72×Scr))was used; Fasting venous blood samples were extracted to detect hemoglobin, serum creatinine, blood cholesterol, blood glucose; Urinary protein was detected by radioimmunoassay.
Results
1 Plasma levels of PMPs and GMP140 were significantly higher in CKD patients than that of in controls(P<0.05).
2 Plasma levels of PMPs and GMP140 in CKD patients among different clinical classification groups: The levels of PMPs in nephritic syndrome group and chronic glomerulonephritis group were significantly higher than that of in control group(P<0.01,P<0.05),The level of PMPs in nephritic syndrome group was significantly higher than that of in hypertensive renal disease group(P <0.05),Other groups had no significant difference(P>0.05).The levels of GMP140 in all groups were significantly higher than that of in control group(P<0.01),The level of GMP140 in nephritic syndrome group was significantly higher than that of in Lupus nephropathy group, Diabetic Nephropathy group and hypertensive renal disease group(P<0.01,P<0.05), The level of GMP140 in chronic glomerulonephritis group was significantly higher than that of in Diabetic Nephropathy group(P<0.01).
3 Plasma levels of PMPs and GMP140 in different stages of CKD: The level of PMPs in stage I was significantly higher than stage IV(P <0.05); Other stages had no significant difference(P >0.05). The level of GMP140 in different stages had no significant difference(P >0.05).
4 As for PMPs, a positive correlation was found with blood pressure(r=0.39,P <0.05), no correlation was found among creatinine clearance(r=-0.15,P >0.05), 24h urinary protein(r=0.18,P >0.05), hemoglobin(r=-0.21,P >0.05), cholesterol(r=0.10,P >0.05),GMP140 has a positive correlation with PMPs(r=0.31,P <0.05).
5 Plasma levels of EMPs and vWF were significantly higher in CKD patients than that of in controls(P<0.01).
6 Plasma levels of EMPs and vWF in different clinical classification groups were significantly higher than that of in control group(P<0.01,P<0.05); The level of EMPs in nephritic syndrome group was significantly higher than that of in hypertensive renal disease group(P<0.05).Meanwhile, the level of vWF in nephritic syndrome group was remarkable higher than that of in hypertensive renal disease group and chronic glomerulonephritis group.Other groups had no significant difference(P >0.05).
7 In different stages of CKD, the level of EMPs in stage I was significantly higher than stage IV(P<0.05), The level of vWF in different stages had no significant difference(P>0.05).
8 As for EMPs, a positive correlation was found with blood pressure(r=0.52,P <0.01), no correlation was found among creatinine clearance(r=-0.12,P>0.05), 24h urinary protein(r=0.15,P>0.05), hemoglobin(r=-0.22,P>0.05), cholestero(lr=0.07,P>0.05). vWF has a positive correlation with EMPs(r=0.41,P<0.05).
Conclusion
1 Patients with chronic kidney disease have platelet activation and endothelial dysfunction. The platelet activation and endothelial dysfunction are participate in the pathophysiological process of the occurrence and development of chronic kidney disease.
2 Hypertension is one of the important reasons for platelet activation and endothelial dysfunction in patients with chronic kidney disease.
3 As a new marker, PMPs and EMPs can be used as a reflection of platelet activation and endothelial function.
方法收集苏州大学附属第一医院肾内科2007年2月至2008年6月住院的慢性肾病患者72例(定义和分期依据K/DOQI慢性肾脏病临床实践指南),健康正常对照组20例。采用流式细胞术检测血浆中PMPs、EMPs的水平;采用酶联免疫吸附试验(ELISA法)检测血浆中GMP140、vWF的水平;检测血压、身高、体重、用Cockcroft-Gault公式法计算肌酐清除率(Ccr(ml/min)=[(140-年龄)×体重×(0.85女性)]/(72×Scr));抽取空腹静脉血检测血红蛋白含量、血肌酐、血胆固醇、血糖;放射免疫法检测微量尿蛋白。
结果
1与对照组比较,慢性肾病组患者血浆PMPs及GMP140的水平均显著升高(P<0.05)。
2慢性肾病患者不同临床分类组之间血浆PMPs、GMP140的水平:肾病综合征组及慢性肾炎组患者血浆PMPs的含量均显著高于对照组(P<0.01,P<0.05),其中肾病综合征组血浆PMPs的含量显著高于高血压肾病组(P<0.05),其余各组间无显著性差异(P>0.05);各临床分类组患者血浆GMP140的含量均显著高于对照组(P<0.01),其中肾病综合征组血浆GMP140的含量显著高于狼疮性肾病组、糖尿病肾病组和高血压肾病组(P<0.01,P<0.05),慢性肾炎组血浆GMP140的含量显著高于糖尿病肾病组(P<0.01)。
3慢性肾病患者不同分期之间血浆PMPs、GMP140水平的比较:I期患者血浆中PMPs含量显著高于IV期(P<0.05),其余各组间无显著性差异(P>0.05);不同的CKD分期间GMP140含量无明显差异(P>0.05)。
4经相关性分析,慢性肾病患者血浆PMPs的水平与血压呈正相关(r=0.39,P <0.05),与肌酐清除率(r=-0.15,P>0.05)、24小时尿蛋白定量(r=0.18,P>0.05)、血红蛋白(r=-0.21,P>0.05)、血胆固醇(r=0.10,P>0.05)的相关性无显著性意义。GMP140的水平与PMPs呈正相关(r=0.31,P<0.05)。
5与对照组比较,慢性肾病组患者血浆EMPs及vWF的水平均显著升高(P<0.01)。
6不同临床类型的CKD患者血浆EMPs及vWF的含量均显著高于对照组(P<0.01,P<0.05),其中肾病综合征组血浆EMPs的含量显著高于高血压肾病组(P <0.05),其余各组间无显著性差异(P>0.05)。肾病综合征组血浆vWF的含量显著高于高血压肾病组及慢性肾炎组,其余各组间无显著性差异(P>0.05)。
7慢性肾病患者不同分期之间血浆EMPs、vWF水平的比较:I期患者血浆中EMPs含量显著高于IV期(P<0.05),其余各组间无显著性差异(P>0.05);不同的CKD分期间vWF含量无明显差异(P>0.05)。
8经相关性分析,vWF的水平与EMPs呈正相关(r=0.41,P<0.05),慢性肾病患者血浆EMPs的水平与血压呈正相关(r=0.52,P<0.01),与肌酐清除率(r=-0.12,P>0.05)、24小时尿蛋白定量(r=0.15,P>0.05)、血红蛋白(r=-0.22,P>0.05)、血胆固醇(r=0.07,P>0.05)的相关性无显著性意义。
结论
1慢性肾病患者存在明显的血小板活化及内皮功能障碍,血小板活化及内皮功能紊乱参与慢性肾病发生发展的病理生理过程。
2高血压是使慢性肾病患者血小板活化及内皮功能异常的重要原因之一。
3 PMPs、EMPs可作为一种反映血小板活化及内皮功能损伤的新标记。
Objective Compare the levels of PMPs、GMP140、EMPs and vWF in patients with chronic kidney disease and in normal control group, to explore the significance of the PMPs and EMPs in chronic kidney disease.
Methods From February 2007 to June 2008, 72 cases of patients with chronic kidney disease who were hospitalized in the First Affiliated Hospital of Suzhou University were enrolled in this study (Definition and phases were based on K / DOQI chronic kidney disease clinical practice guidelines) ,20 cases of healthy controls were also enrolled. Circulating PMPs and EMPs were numerated by flow cytometry;GMP140 and vWF were measured by the enzyme-linked immunosorbent assay; The blood pressure, height and weight of all subjects were measured also.The Cockcroft-Gault formula to calculate creatinine clearance (Ccr (ml / min) = [(140 - age)×weight×(0.85 for women)] / (72×Scr))was used; Fasting venous blood samples were extracted to detect hemoglobin, serum creatinine, blood cholesterol, blood glucose; Urinary protein was detected by radioimmunoassay.
Results
1 Plasma levels of PMPs and GMP140 were significantly higher in CKD patients than that of in controls(P<0.05).
2 Plasma levels of PMPs and GMP140 in CKD patients among different clinical classification groups: The levels of PMPs in nephritic syndrome group and chronic glomerulonephritis group were significantly higher than that of in control group(P<0.01,P<0.05),The level of PMPs in nephritic syndrome group was significantly higher than that of in hypertensive renal disease group(P <0.05),Other groups had no significant difference(P>0.05).The levels of GMP140 in all groups were significantly higher than that of in control group(P<0.01),The level of GMP140 in nephritic syndrome group was significantly higher than that of in Lupus nephropathy group, Diabetic Nephropathy group and hypertensive renal disease group(P<0.01,P<0.05), The level of GMP140 in chronic glomerulonephritis group was significantly higher than that of in Diabetic Nephropathy group(P<0.01).
3 Plasma levels of PMPs and GMP140 in different stages of CKD: The level of PMPs in stage I was significantly higher than stage IV(P <0.05); Other stages had no significant difference(P >0.05). The level of GMP140 in different stages had no significant difference(P >0.05).
4 As for PMPs, a positive correlation was found with blood pressure(r=0.39,P <0.05), no correlation was found among creatinine clearance(r=-0.15,P >0.05), 24h urinary protein(r=0.18,P >0.05), hemoglobin(r=-0.21,P >0.05), cholesterol(r=0.10,P >0.05),GMP140 has a positive correlation with PMPs(r=0.31,P <0.05).
5 Plasma levels of EMPs and vWF were significantly higher in CKD patients than that of in controls(P<0.01).
6 Plasma levels of EMPs and vWF in different clinical classification groups were significantly higher than that of in control group(P<0.01,P<0.05); The level of EMPs in nephritic syndrome group was significantly higher than that of in hypertensive renal disease group(P<0.05).Meanwhile, the level of vWF in nephritic syndrome group was remarkable higher than that of in hypertensive renal disease group and chronic glomerulonephritis group.Other groups had no significant difference(P >0.05).
7 In different stages of CKD, the level of EMPs in stage I was significantly higher than stage IV(P<0.05), The level of vWF in different stages had no significant difference(P>0.05).
8 As for EMPs, a positive correlation was found with blood pressure(r=0.52,P <0.01), no correlation was found among creatinine clearance(r=-0.12,P>0.05), 24h urinary protein(r=0.15,P>0.05), hemoglobin(r=-0.22,P>0.05), cholestero(lr=0.07,P>0.05). vWF has a positive correlation with EMPs(r=0.41,P<0.05).
Conclusion
1 Patients with chronic kidney disease have platelet activation and endothelial dysfunction. The platelet activation and endothelial dysfunction are participate in the pathophysiological process of the occurrence and development of chronic kidney disease.
2 Hypertension is one of the important reasons for platelet activation and endothelial dysfunction in patients with chronic kidney disease.
3 As a new marker, PMPs and EMPs can be used as a reflection of platelet activation and endothelial function.
引文
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14. Bernal-Mizrachi L,Jy W,Fierro C,et al. Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes. Int J Cardiol. 2004,97(3):439-446.
15. Garcia S,Chirinos J,Jimenez J,et al. Phenotypic assessment of endothelial microparticles in patients with heart failure and after heart transplantation: switch from cell activation to apoptosis. J Heart Lung Transplant.2005,24(12):2184-2189.
16. Dignat-George F,Camoin-Jau L,Sabatier F,et al. Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome. Thromb and Haemost.2004,91(4):667–673.
17. Larkin M,Raised endothelial microparticles an early marker for multiple sclerosis? Lancet. 2001,357(9269):1679.
18. Combes V,Simon AC,Grau GE,et al. In vitro gene ration of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest. 1999,104(1):93–102.
19. Ogura H,Tanaka H,Koh T,et al. Enhanced production of endothelial microparticles with increased binding to leukocytes in patients with severe systemic inflammatory response syndrome. J Trauma, 2004,56(4):823–830.
20. Jimenez JJ,Jy W,Mauro LM,et al.Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation. Br J Haematol, 2003,123(5):896–902.
21. Gonzalez-Quintero VH,Smarkusky LP,Jimenez JJ,et al. Elevated plasma endothelial microparticles: preeclampsia versus gestational hypertension. American J Obstet Gynecol. 2004,191(4):1418-1424.
22. Soriano AO, Jy W, Chirinos JA, et al. Levels of endothelial and platelet microparticles and their interactions with leukocytes negatively correlate with organ dysfunction and predict mortality in severe sepsis. Crit Care Med. 2005,33(11):2540-2546.
23. Densmore JC,Signorino PR,Ou J,et al. Endothelium-derived microparticles induce endothelial dysfunction and acute lung injury. Shock. 2006,26(5):464-471.