Adal Y, Pratt L, Comper W D
Biochemistry Department, Monash University, Clayton, Victoria, Australia.
Microcirculation. 1994 Oct;1(3):169-74. doi: 10.3109/10739689409148271.
The renal fractional clearance of [3H]DEAE dextran has been widely used to substantiate the charge selective model for renal permselectively, although there has only been one reported study on this type of clearance. This study sets out to examine the fractional clearance and glomerular processing of DEAE dextran.
Fractional clearance studies were performed using isolated perfused rat kidneys. The glomerular processing of DEAE dextran was assessed by examining the kinetics of DEAE dextran uptake in glomeruli isolated post perfusion.
The fractional clearance of DEAE dextran used in the concentration range of 15-150 micrograms/ml in the perfusate of the isolated perfused kidney did not produce the classical in vivo facilitated transport of DEAE dextran as compared to dextran as observed by Bohrer et al. The fractional clearance curve displays retarded clearance of low molecular weight (small radii) DEAE dextran, giving the appearance of a 'flat curve'. Similar results were obtained when an oxygen free radical scavenger cocktail was included in the perfusate. These results may be due to the fact that DEAE dextran binds to the glomeruli (at an order of magnitude greater than dextran sulfate). Perfused kidneys with [3H]DEAE dextran for 1 h followed by a five minute perfusion with unlabelled DEAE dextran revealed no significant change in the glomerular levels of [3H]DEAE dextran (unlike dextran sulfate). Perfusion of rat kidneys with 15 micrograms/ml DEAE dextran produced no changes in the electron microscopical morphology of the glomerulus and no changes in the fractional clearance of dextran.
These results do not support the glomerular charge selectivity model that involves a non-binding electrostatic interaction of the charged dextran with the fixed anion charges of the glomerular capillary wall.
尽管关于[3H]二乙氨基乙基葡聚糖(DEAE葡聚糖)的肾分数清除率仅有一项报道研究,但它已被广泛用于证实肾脏选择性通透的电荷选择性模型。本研究旨在检测DEAE葡聚糖的分数清除率及肾小球处理情况。
采用离体灌注大鼠肾脏进行分数清除率研究。通过检测灌注后分离出的肾小球中DEAE葡聚糖摄取动力学来评估其肾小球处理情况。
与Bohrer等人观察到的葡聚糖相比,在离体灌注肾脏灌注液中使用浓度范围为15 - 150微克/毫升的DEAE葡聚糖时,其分数清除率并未产生经典的体内促进转运现象。分数清除率曲线显示低分子量(小半径)DEAE葡聚糖的清除延迟,呈现出“平坦曲线”的外观。当灌注液中加入氧自由基清除剂混合物时,也得到了类似结果。这些结果可能是由于DEAE葡聚糖与肾小球结合(结合量比硫酸葡聚糖大一个数量级)。用[3H]DEAE葡聚糖灌注肾脏1小时,随后用未标记的DEAE葡聚糖灌注5分钟,结果显示[3H]DEAE葡聚糖的肾小球水平无显著变化(与硫酸葡聚糖不同)。用15微克/毫升DEAE葡聚糖灌注大鼠肾脏,肾小球的电子显微镜形态无变化,葡聚糖的分数清除率也无变化。
这些结果不支持涉及带电荷葡聚糖与肾小球毛细血管壁固定阴离子电荷发生非结合性静电相互作用的肾小球电荷选择性模型。