Sverrisson Kristinn, Axelsson Josefin, Rippe Anna, Asgeirsson Daniel, Rippe Bengt
Department of Nephrology, Lund University, Lund, Sweden.
Department of Nephrology, Lund University, Lund, Sweden
Am J Physiol Renal Physiol. 2015 Nov 1;309(9):F800-6. doi: 10.1152/ajprenal.00111.2015. Epub 2015 Aug 19.
This study was performed to investigate the immediate actions of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 on the permeability of the glomerular filtration barrier (GFB) in rats and to test whether these actions are dependent upon the release of reactive oxygen species (ROS). In anesthetized rats, blood access was achieved and the left ureter was cannulated for urine collection. Rats were continuously infused intravenously with either IL-1β (0.4 and 2 μg·kg(-1)·h(-1)), TNF-α (0.4 and 2 μg·kg(-1)·h(-1)), or IL-6 (4 and 8 μg·kg(-1)·h(-1)), together with polydisperse FITC-Ficoll-70/400 and inulin for 1 h. Plasma and urine samples were analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ). The glomerular filtration rate (GFR) was also assessed (51Cr-EDTA). In separate experiments, the superoxide scavenger tempol (30 mg·kg(-1)·h(-1)) was given before and during cytokine infusions. IL-1β and TNF-α caused rapid, partly reversible increases in glomerular permeability to large molecules (Ficoll50-80Å), peaking at 5-30 min, while IL-6 caused a more gradual increase in permeability, leveling off at 60 min. Tempol almost completely abrogated the glomerular permeability effects of the cytokines infused. In conclusion IL-1β, TNF-α, and IL-6, when infused systemically, caused immediate and partly reversible increases in glomerular permeability, which could be inhibited by the superoxide scavenger tempol, suggesting an important role of ROS in acute cytokine-induced permeability changes in the GFB.
本研究旨在探讨促炎细胞因子白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）对大鼠肾小球滤过屏障（GFB）通透性的即时作用，并测试这些作用是否依赖于活性氧（ROS）的释放。在麻醉的大鼠中，建立血液通路并插入左输尿管以收集尿液。大鼠连续静脉输注IL-1β（0.4和2μg·kg⁻¹·h⁻¹）、TNF-α（0.4和2μg·kg⁻¹·h⁻¹）或IL-6（4和8μg·kg⁻¹·h⁻¹），同时输注多分散的异硫氰酸荧光素-菲可（FITC-Ficoll）-70/400和菊粉1小时。通过高效体积排阻色谱法（HPSEC）分析血浆和尿液样本，以测定肾小球滤过系数（θ）。还评估了肾小球滤过率（GFR）（⁵¹Cr-乙二胺四乙酸）。在单独的实验中，在细胞因子输注前和输注期间给予超氧化物清除剂tempol（30mg·kg⁻¹·h⁻¹）。IL-1β和TNF-α导致肾小球对大分子（菲可50 - 80Å）的通透性迅速、部分可逆地增加，在5 - 30分钟达到峰值，而IL-6导致通透性更逐渐增加，在60分钟时趋于平稳。Tempol几乎完全消除了所输注细胞因子对肾小球通透性的影响。总之，IL-1β、TNF-α和IL-6全身输注时会导致肾小球通透性立即且部分可逆地增加，这可被超氧化物清除剂tempol抑制，表明ROS在急性细胞因子诱导的GFB通透性变化中起重要作用。
