辛伐他汀抑制原发性肾病综合征患者外周血单个核细胞组织因子及纤溶酶原激活物抑制剂-1的分泌。

Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 secretion by peripheral blood mononuclear cells in patients with primary nephrotic syndrome.

作者信息

Wei Jia-li, Cui Hui-ming, Ma Chun-yang

机构信息

Department of Neurology, The Second Xiangya Hospital of Central South University, Hunan, PR China.

出版信息

Eur J Med Res. 2007 May 29;12(5):216-21.

PMID:17513194

Abstract

BACKGROUND

Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) activity and/or expression are upregulated in nephrotic syndrome. Despite extensive research on antithrombotic effect of statins, little is known about their effects on TF and PAI-1 expression in peripheral blood mononuclear cells in patients with primary nephrotic syndrome(PNS).

METHODS

PBMCs were isolated by gradient centrifugation from 25 individuals with PNS and 25 healthy subjects. TF and PAI-1 mRNA were detected by RT-PCR. The activities of TF and PAI-1 were determined with ELISA and chromogenic substrate method, respectively. The patients with PNS were then treated with simvastatin 40 mg/day for 2 weeks. The activities of TF, PAI-1 and TF, PAI-1 mRNA of PBMCs were also measured.

RESULTS

Compared with controls, patients with PNS had increased TF, PAI-1 secretion by PBMCs at baseline (70.4 +/- 15.6 ng/l vs. 32.7 +/- 8.2 ng/l; 15.9 +/- 2.4 (x10(3) AU/l) vs. 3.9 +/- 1.5(x10(3) AU/l), P<0.01) and after stimulated by LPS (10 ng/mL) (89.2 +/- 13.4 ng/l vs. 49.5 +/- 10.3 ng/l; 23.8 +/- 3.3 (x10(3) AU/l) vs. 8.1 +/- 2.1, P<0.01). The simvastatin treatment resulted in a significant effect in decreasing TF and PAI-1 (69.1 +/- 14.6 ng/l vs. 89.2 +/- 13.4 ng/l; 16.5 +/- 4.8 (x10(3) AU/l) vs. 23.8 +/- 3.3 (x10(3) AU/l), P<0.05) secretion in PBMCs. Increased TF and PAI-1 mRNA expression in PBMCs from PNS (1.034 +/- 0.043 and 0.982 +/- 0.056, respectively) as compared to the control (0.221 +/- 0.015 and 0.221 +/- 0.015, respectively) (p<0.01). two-week simvastatin treatment resulted in significant decrease of TF (0.535 +/- 0.028, p<0.01) and PAI-1 mRNA (0.602 +/- 0.037, p<0.01).

CONCLUSION

TF and PAI-1 mRNA expression and activities in PBMCs were increased in PNS. Simvastatin reduced TF and PAI-1 expression and activity in PBMCs. These effects may partially be relevant to the clinical benefits of statins in the treatment of PNS.

摘要

背景

组织因子（TF）和纤溶酶原激活物抑制剂-1（PAI-1）的活性和/或表达在肾病综合征中上调。尽管对他汀类药物的抗血栓作用进行了广泛研究，但对于它们对原发性肾病综合征（PNS）患者外周血单个核细胞中TF和PAI-1表达的影响知之甚少。

方法

通过梯度离心从25例PNS患者和25名健康受试者中分离外周血单个核细胞（PBMC）。采用逆转录聚合酶链反应（RT-PCR）检测TF和PAI-1 mRNA。分别用酶联免疫吸附测定（ELISA）和发色底物法测定TF和PAI-1的活性。然后对PNS患者给予辛伐他汀40mg/天治疗2周。同时检测PBMC中TF、PAI-1的活性以及TF、PAI-1 mRNA。

结果

与对照组相比，PNS患者基线时PBMC分泌的TF、PAI-1增加（70.4±15.6 ng/l对32.7±8.2 ng/l；15.9±2.4（×10³AU/l）对3.9±1.5（×10³AU/l），P<0.01），经脂多糖（LPS，10 ng/mL）刺激后也增加（89.2±13.4 ng/l对49.5±10.3 ng/l；23.8±3.3（×10³AU/l）对8.1±2.1，P<0.01）。辛伐他汀治疗显著降低了PBMC中TF和PAI-1的分泌（69.1±14.6 ng/l对89.2±13.4 ng/l；16.5±4.8（×10³AU/l）对23.8±3.3（×10³AU/l），P<0.05）。与对照组相比，PNS患者PBMC中TF和PAI-1 mRNA表达增加（分别为1.034±0.043和0.982±0.056）（对照组分别为0.221±0.015和0.221±0.015）（P<0.01）。辛伐他汀治疗2周后，TF（0.535±0.028，P<0.01）和PAI-1 mRNA（0.602±0.037，P<0.01）显著降低。