Renal pro-inflammatory cytokine gene expression in diabetic nephropathy:: Effect of angiotensin-converting enzyme inhibition and pentoxifylline administration
Renal pro-inflammatory cytokine gene expression in diabetic nephropathy:: Effect of angiotensin-converting enzyme inhibition and pentoxifylline administration
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DOI：
10.1159/000098004
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发表时间：
2006-01-01
影响因子：
4.2
通讯作者：
Garcia, Javier
中科院分区：
文献类型：
--
作者：
Navarro, Juan F.;Milena, Francisco J.;Garcia, Javier
背景：近年来的研究表明，炎症在糖尿病肾病（DN）的发病机制中起重要作用。肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1和IL-6是具有普遍促炎活性的细胞因子。本研究旨在探讨DN患者肾组织中TNF-α、IL-1和IL-6的基因表达及其与尿白蛋白排泄（UAE）的关系。此外，我们还研究了血管紧张素转换酶抑制剂和戊茶碱（PTF）给药对这些参数的影响。方法：建立链脲佐菌素诱导的糖尿病大鼠模型，分别给予依那普利（EN）或PTF治疗8周。通过实时聚合酶链反应评价肾促炎细胞因子的表达。还评价了尿细胞因子排泄和白蛋白尿。结果如下：未治疗糖尿病大鼠肾皮质TNF-α、IL-1和IL-6的mRNA表达分别是非糖尿病大鼠的2.4倍、1.2倍和3.4倍。肾脏重量和UAE与肾脏TNF-α和IL-6的mRNA表达显著相关。EN和PTF给药实际上消除了TNF-α、IL-1和IL-6的过度表达，这与肾重量和尿白蛋白排泄的减少有关。结论：DN时肾脏主要促炎细胞因子TNF-α、IL-1和IL-6表达增加，与UAE显著相关。EN和PTF给药阻止了这种增强的表达，导致尿细胞因子排泄减少和白蛋白尿减少。这些发现为DN的发病机制提供了新的见解，支持炎症机制在糖尿病继发性肾损伤中发挥作用的假设。版权所有（c）2006 S. Karger AG，巴塞尔。
Background: Recent studies have shown a role for inflammation in the pathogenesis of diabetic nephropathy (DN). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 and IL-6 are cytokines with a prevalent pro-inflammatory activity. Our objective was to study the renal gene expression of TNF-alpha, IL-1 and IL-6 in DN and their relationship with renal damage assessed by urinary albumin excretion (UAE). In addition, we also investigated the effect of angiotensin-converting enzyme inhibition and pentoxifylline (PTF) administration on these parameters. Methods: After streptozotocin-induced diabetes, rats received either no treatment or therapy with enalapril (EN) or PTF for 8 weeks. Renal expression of proinflammatory cytokines was evaluated by real-time polymerase chain reaction. Urinary cytokine excretion and albuminuria were also evaluated. Results: Renal cortical mRNA expression for TNF-alpha, IL-1 and IL-6 in untreated diabetic rats was 2.4-, 1.2- and 3.4-fold higher than in non-diabetic rats. Kidney weight and UAE were significantly associated with renal mRNA expression of TNF-alpha and IL-6. Both EN and PTF administration virtually abrogated the overexpression of TNF-alpha, IL-1 and IL-6, which was associated with a reduction in kidney weight and urinary albumin excretion. Conclusion: The renal expression of the main pro-inflammatory cytokines TNF-alpha, IL-1 and IL-6 is increased in DN, which is significantly associated with UAE. EN and PTF administration prevented this enhanced expression, leading to a decrease in urinary cytokine excretion and a reduction in albuminuria. These findings provide novel insight into the pathogenic mechanisms of DN, supporting the hypothesis that inflammatory mechanisms play a role in the renal injury secondary to diabetes mellitus. Copyright (c) 2006 S. Karger AG, Basel.