Wei Jia-li, Cui Hui-ming, Ma Chun-yang
Department of Neurology, The Second Xiangya Hospital of Central South University, Hunan, PR China.
Eur J Med Res. 2007 May 29;12(5):216-21.
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).
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.
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).
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.
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。
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。
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。
PNS患者PBMC中TF和PAI-1 mRNA表达及活性增加。辛伐他汀可降低PBMC中TF和PAI-1的表达及活性。这些作用可能部分与他汀类药物治疗PNS的临床益处相关。
