Madsen Mia Gebauer, Nørregaard Rikke, Stødkilde Lene, Christensen Jane Hvarregaard, Jørgensen Troels Munch, Frøkiær Jørgen
Department of Urology, Paediatric Section, Aarhus University Hospital, Skejby, Aarhus, Denmark.
Scand J Urol Nephrol. 2012 Apr;46(2):91-6. doi: 10.3109/00365599.2011.637958. Epub 2011 Dec 12.
In search of potential urinary biomarkers of obstructive nephropathy, this study examined whether a potential change in the concentration of urinary cytokines [interferon-γ(IFN-γ), interleukin-1β (IL-1β), IL-2, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)] reliably reflects changes in renal parenchymal levels of the same cytokines following the release of acute and chronic unilateral ureteral obstruction, respectively.
Acute obstruction was performed in 12 adult rats. After 48 h, six rats were used for selective urine collection and six rats had their kidneys removed and dissected into inner medulla and cortex. Chronic obstruction was performed in newborn rats. After 10 weeks, a similar set-up to that of the acute study was implemented. Sham-operated rats were prepared in parallel. Urine and tissue cytokines were measured with a bead-based multiplex sandwich immunoassay and analysed on a Luminex 100 IS instrument.
In the acute study, there were significantly increased concentrations of IL-1β and IL-6 in inner medulla and in urine from the obstructed kidney, significantly increased concentrations of TNF-α in urine from the obstructed kidney and, importantly, significantly increased levels of IL-10 in cortex and in urine from the non-obstructed kidney. In the chronic study, there were similar changes in IL-1β and IL-6 (not significant) but no changes in TNF-α and IL-10.
This study showed that inflammatory cytokines can be detected both in renal parenchyma and in urine from rats with experimental unilateral ureteral obstruction. Further studies are needed to confirm the diagnostic accuracy of IL-1β, IL-6, IL-10 and TNF-α in urine.
为寻找梗阻性肾病潜在的尿液生物标志物，本研究分别检测了急性和慢性单侧输尿管梗阻解除后，尿液中细胞因子[干扰素-γ（IFN-γ）、白细胞介素-1β（IL-1β）、IL-2、IL-6、IL-10和肿瘤坏死因子-α（TNF-α）]浓度的潜在变化是否能可靠反映同一细胞因子在肾实质中的水平变化。
对12只成年大鼠进行急性梗阻。48小时后，6只大鼠用于选择性尿液收集，6只大鼠摘除肾脏并分别解剖为内髓质和皮质。对新生大鼠进行慢性梗阻。10周后，采用与急性研究相似的设置。同时制备假手术大鼠。采用基于微珠的多重夹心免疫分析法测定尿液和组织中的细胞因子，并在Luminex 100 IS仪器上进行分析。
在急性研究中，梗阻侧肾脏内髓质和尿液中IL-1β和IL-6浓度显著升高，梗阻侧肾脏尿液中TNF-α浓度显著升高，重要的是，非梗阻侧肾脏皮质和尿液中IL-10水平显著升高。在慢性研究中，IL-1β和IL-6有类似变化（不显著），但TNF-α和IL-10无变化。
本研究表明，在实验性单侧输尿管梗阻大鼠的肾实质和尿液中均可检测到炎性细胞因子。需要进一步研究以证实尿液中IL-1β、IL-6、IL-10和TNF-α的诊断准确性。
