Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Department of Immunology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8613-8618. doi: 10.3892/mmr.2017.7697. Epub 2017 Oct 3.
Low molecular weight heparin (LMWH) has a structure similar to heparan sulfate, which exerts anti‑inflammatory effects via inhibiting elastase (Ela) activity. Release of Ela along the glomerular capillary wall may induce glomerular injury and proteinuria. The present study aimed to investigate the influence of LMWH on steroid‑sensitive nephrotic syndrome (SSNS) and the potential underlying mechanism. A total of 40 SSNS patients and 20 healthy controls were recruited. SSNS patients were treated with LMWH and prednisone simultaneously (LMWH+pred group) or with prednisone alone (pred group). Proteinuria, urinary glycosaminoglycans (GAGs), serum Ela and urinary creatinine levels were measured. The nephrotic period of SSNS was 15.93±5.78 days. The nephrotic period of SSNS in LMWH+pred group was significantly reduced compared with the pred group (14.13±4.56 vs. 18.63±6.49 days; P<0.05). At the follow‑up of the SSNS patients, there was no statistically significant difference in number of relapses between the LMWH+pred and pred groups. Proteinuria (2.51±0.97 g/24 h), urinary GAG levels (4.92±0.87 mg/mmol creatinine) and serum Ela levels (77.64±10.99 ng/l) were significantly greater in the nephrotic period of SSNS compared with the remission period (0.107±0.026 g/24 h, 1.53±0.27 mg/mmol Cr and 41.92±7.81 ng/l, respectively) and the healthy control group (0.098±0.027 g/24 h, 1.40±0.26 mg/mmol creatinine and 38.43±9.83 ng/l, respectively; P<0.05). During the remission period, urinary GAG and serum Ela levels in the LMWH+pred group were significantly reduced compared with the pred group (P<0.05), whereas proteinuria did not differ between these groups (P>0.05). Positive correlations were revealed between urinary GAG excretion and proteinuria (r=0.877; P<0.05), proteinuria and serum Ela levels (r=0.844; P<0.05) and serum Ela levels and urinary GAG excretion (r=0.881; P<0.05). The results of the present study indicated that elevated serum Ela levels may induce proteinuria by degrading GAGs in the glomerular basement membrane in children with SSNS. LMWH may benefit nephrotic remission of SSNS via inhibiting Ela.
低分子量肝素(LMWH)的结构与肝素硫酸盐相似,通过抑制弹性蛋白酶(Ela)活性发挥抗炎作用。沿着肾小球毛细血管壁释放的弹性蛋白酶可能会诱导肾小球损伤和蛋白尿。本研究旨在探讨 LMWH 对类固醇敏感型肾病综合征(SSNS)的影响及其潜在机制。
共纳入 40 例 SSNS 患者和 20 例健康对照者。SSNS 患者同时接受 LMWH 和泼尼松龙治疗(LMWH+pred 组)或单独接受泼尼松龙治疗(pred 组)。测量蛋白尿、尿糖胺聚糖(GAG)、血清 Ela 和尿肌酐水平。SSNS 的肾病期为 15.93±5.78 天。与 pred 组相比,LMWH+pred 组的 SSNS 肾病期明显缩短(14.13±4.56 与 18.63±6.49 天;P<0.05)。在 SSNS 患者随访时,LMWH+pred 组和 pred 组的复发例数无统计学差异。与缓解期(0.107±0.026 g/24 h)和健康对照组(0.098±0.027 g/24 h)相比,SSNS 肾病期患者的蛋白尿(2.51±0.97 g/24 h)、尿 GAG 水平(4.92±0.87 mg/mmol 肌酐)和血清 Ela 水平(77.64±10.99 ng/l)显著更高(分别为 4.92±0.87 mg/mmol Cr 和 38.43±9.83 ng/l;P<0.05)。在缓解期,与 pred 组相比,LMWH+pred 组的尿 GAG 和血清 Ela 水平显著降低(P<0.05),而两组间的蛋白尿无差异(P>0.05)。尿 GAG 排泄与蛋白尿呈正相关(r=0.877;P<0.05),蛋白尿与血清 Ela 水平呈正相关(r=0.844;P<0.05),血清 Ela 水平与尿 GAG 排泄呈正相关(r=0.881;P<0.05)。
本研究结果表明,血清 Ela 水平升高可能通过降解肾小球基底膜中的 GAG 诱导 SSNS 患儿蛋白尿。LMWH 通过抑制 Ela 可能有益于 SSNS 的肾病缓解。