Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model.
Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model.
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DOI：
10.14814/phy2.12397
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发表时间：
2015-05
影响因子：
2.5
通讯作者：
Bakoush O
中科院分区：
文献类型：
--
作者：
Lubbad L;Öberg CM;Dhanasekaran S;Nemmar A;Hammad F;Pathan JY;Rippe B;Bakoush O
微量白蛋白尿是糖尿病肾病的早期表现。这种情况的潜在贡献者是肾小球滤过屏障（GFB）的大小和电荷选择性降低，以及滤过蛋白质的肾小管重吸收受损。然而，最近有报道称，在早期实验性糖尿病肾病中，GFB的电荷选择性没有显著改变。本研究旨在应用一种新型的分布式双孔模型研究大鼠长期1型糖尿病时GFB的功能变化。我们检测了15只链脲佐菌素（STZ）诱导的糖尿病（血糖≤ 20 mmol/L）至少3个月的雄性Wistar大鼠和年龄匹配的对照大鼠的肾小球通透性。通过使用尺寸排阻HPLC测定FITC-Ficoll（分子半径20-90 μ m）的肾小球筛分系数（θ），评估肾小球渗透性的变化。与年龄匹配的对照组相比，STZ-糖尿病大鼠中半径>50 μ m的FITC-Ficoll的θ值显著增加（50-69 ° θ = 0.001 vs. 0.0002，70-90 ° θ = 0.0007 vs. 0.00006，P < 0.001），而FITC-Ficoll <50 μ g的θ在糖尿病大鼠中倾向于低于对照组（36-49 μ g的θ = 0.013 vs. 0.016，ns）。根据分布式双孔模型，主要是增加了大分子运输通过大孔在肾小球过滤器的糖尿病大鼠与损失的小孔面积。由于大孔的数量和尺寸扩展的增加而导致的肾小球尺寸选择性的恶化，而小孔系统的渗透性没有变化，代表了诱导实验性糖尿病3个月后观察到的主要功能变化。
Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ∼20 mmol/L) and in age-matched control rats. The changes in glomerular permeability were assessed by determining the glomerular sieving coefficients (θ) for FITC-Ficoll (molecular radius 20–90 Å) using size exclusion HPLC. The values of θ for FITC-Ficoll of radius >50 Å were significantly increased in STZ-diabetic rats compared to age-matched controls (θ for 50–69 Å = 0.001 vs. 0.0002, and θ for 70–90 Å = 0.0007 vs. 0.00006, P < 0.001), while θ for FITC-Ficoll <50 Å tended to be lower in diabetic rats than in controls (θ for 36–49 Å = 0.013 vs. 0.016, ns). According to the distributed two-pore model, there was primarily an increase in macromolecular transport through large pores in the glomerular filter of diabetic rats associated with a loss of small-pore area. Deterioration in the glomerular size selectivity due to an increase in the number and size-spread of large pores, with no changes in the permeability of the small-pore system, represent the major functional changes observed after 3 months of induced experimental diabetes.