Raij L, Keane W F, Osswald H, Michael A
J Clin Invest. 1979 Nov;64(5):1204-12. doi: 10.1172/JCI109574.
The kinetics for mesangial uptake and transport of radiolabeled aggregated human immunoglobulin (Ig)G (AHIgG(125)I) deviated markedly from normal in male Sprague-Dawley rats with ureteral obstruction. Four experimental groups, each containing 25 rats, were used: (a) bilateral ureteral ligation (BUL) with release of one ureter 24 h later; (b) unilateral ureteral ligation with release 24 h later [UUL(R)]; (c) unilateral ureteral ligation without release (unreleased) [UUL(U)]; (d) uremia-control, which consisted of rats with ligated left ureter and a severed right ureter. A similar number of sham-operated rats served as control for each group. AHIgG(125)I (45 mg/100 g body wt) was given intravenously 1 h after release of the ureteral obstruction (25 h after ureteral obstruction or sham surgery). Groups of five control and five experimental animals were sacrificed at 2, 4, 8, 16, and 24 h after injection. At all time intervals, concentrations of AHIgG(125)I in isolated glomeruli from control animals were similar to values obtained from nonobstructed kidneys of UUL(U) and UUL(R) rats: a linear decrease in concentration over a period of 24 h was observed when the logarithm of glomerular AHIgG(125)I concentration was plotted against time. Aberrations in the kinetics were apparent in obstructed kidneys but not in liver, spleen, or blood concentrations of AHIgG(125)I: (a) At 2 h in all obstructed kidneys, glomerular concentration of AHIgG(125)I was markedly reduced. (b) In BUL (released or unreleased), glomerular concentrations of AHIgG(125)I from 4 to 16 h were congruent with 10-fold those in UUL(U) or UUL(R) kidneys. (c) The significant decline in glomerular concentration between 4 and 16 h in control and nonobstructed kidneys was not observed in UUL(R), UUL(U), or BUL (released or unreleased) kidneys; in all obstructed kidneys, a plateau in glomerular concentrations of AHIgG(125)I was observed between 4 and 16 h. (d) After 16 h at a time when the blood level of AHIgG(125)I had decreased to 3% of initial values, there was progressive fall in glomerular AHIgG(125)I. Similar results were obtained in the uremia-control group in rats, which indicated that uremia per se had no measurable effect on mesangial kinetics. These studies demonstrate that ureteral occlusion induces alterations in mesangial uptake (afferent limb) and egress (efferent limb) of macromolecules. Particularly evident is the "blockade" of the efferent limb which is demonstrable at high blood levels of AHIgG(125)I. These alterations in the transit of macromolecules through the mesangium may be mediated in part by the hemodynamic changes that accompany ureteral obstruction.
在输尿管梗阻的雄性斯普拉格 - 道利大鼠中，系膜对放射性标记的聚合人免疫球蛋白（Ig）G（AHIgG(125)I）的摄取和转运动力学明显偏离正常。使用了四个实验组，每组包含25只大鼠：（a）双侧输尿管结扎（BUL），24小时后松开一侧输尿管；（b）单侧输尿管结扎，24小时后松开[UUL(R)]；（c）单侧输尿管结扎且不松开（未松开）[UUL(U)]；（d）尿毒症对照组，由左侧输尿管结扎且右侧输尿管切断的大鼠组成。每组有数量相近的假手术大鼠作为对照。在输尿管梗阻松开后1小时（输尿管梗阻或假手术后25小时）静脉注射AHIgG(125)I（45 mg/100 g体重）。在注射后2、4、8、16和24小时处死每组5只对照动物和5只实验动物。在所有时间间隔，对照动物分离肾小球中AHIgG(125)I的浓度与UUL(U)和UUL(R)大鼠未梗阻肾脏获得的值相似：当绘制肾小球AHIgG(125)I浓度的对数与时间的关系图时，观察到在24小时内浓度呈线性下降。梗阻肾脏中动力学出现异常，但AHIgG(125)I在肝脏、脾脏或血液中的浓度未出现异常：（a）在所有梗阻肾脏中，2小时时肾小球中AHIgG(125)I的浓度显著降低。（b）在BUL组（松开或未松开）中，4至16小时肾小球中AHIgG(125)I的浓度是UUL(U)或UUL(R)肾脏中浓度的10倍。（c）在对照和未梗阻肾脏中4至16小时肾小球浓度的显著下降在UUL(R)、UUL(U)或BUL组（松开或未松开）的肾脏中未观察到；在所有梗阻肾脏中，4至16小时肾小球中AHIgG(125)I的浓度出现平台期。（d）16小时后，当AHIgG(125)I的血液水平降至初始值的3%时，肾小球中AHIgG(125)I逐渐下降。在大鼠尿毒症对照组中获得了类似结果，这表明尿毒症本身对系膜动力学没有可测量的影响。这些研究表明，输尿管阻塞会导致大分子在系膜摄取（传入支）和流出（传出支）方面发生改变。特别明显的是传出支的“阻断”，这在AHIgG(125)I血液水平较高时可以观察到。大分子通过系膜的这些转运改变可能部分由输尿管梗阻伴随的血流动力学变化介导。
