Caulfield J P, Farquhar M G
J Exp Med. 1975 Jul 1;142(1):61-83. doi: 10.1084/jem.142.1.61.
Graded dextrans were used as tracers to study glomerular permeability in nephrotic rats. Two narrow range fractions were used, one which was approximately the same size as albumin (62,000 mol wt) and one which was considerably larger (125,000 mol wt). Nephrosis was induced with daily injections of an aminonucleoside of puromycin, and the animals examined after 7 days, when proteinuria is minimal, or after 10 days, when proteinuria has almost reached a maximum. At both stages and with both dextran fractions the following results were obtained: (a) dextran was retained for up to 3 h (the longest interval studied) in the plasma at high concentration; (b) there was a sharp drop in the concentration of tracer between the inner, looser portions of the basement membrane (lamina rara interna) and its outer denser portions (lamina densa), (c) accumulation of dextran was seen in the mesangial areas with time; and (d) no accumulation of dextran was seen in the slits at any time. These results are the same as those reported earlier in normal animals, and they demonstrate that in nephrotics the basement membrane still behaves as the main filtration barrier retaining most of the plasma proteins. Certain differences from the findings in normals were also noted in that increased amounts of the tracer were present on the epithelial side of the basement membrane: (a) in the urinary spaces; (b) in the subepithelial portions of the basement membrane; and (c) within lysosomes (protein absorption droplets) in the epithelial cytoplasm. In addition areas of thinning of the dense portions of the basement membrane (lamina densa) were seen which were accompanied by a corresponding widening of the less dense, subendothelial and subepithelial layers (lamina rara interna and externa, respectively). The presence of increased quantities of dextran on the epithelial side of the basement membrane indicates that the filter, i.e. the basement membrane, is leaky and allows increased passage of dextrans and therefore plasma proteins.
用分级葡聚糖作为示踪剂来研究肾病大鼠的肾小球通透性。使用了两个窄分子量范围的级分，一个与白蛋白大小近似（分子量62,000），另一个则大得多（分子量125,000）。通过每日注射嘌呤霉素氨基核苷诱导肾病，在7天（蛋白尿最小时）或10天（蛋白尿几乎达到最大值时）后对动物进行检查。在这两个阶段，使用两种葡聚糖级分均得到了以下结果：(a) 葡聚糖在血浆中高浓度保留长达3小时（研究的最长间隔时间）；(b) 示踪剂浓度在基底膜内侧较疏松部分（内疏松层）与其外侧较致密部分（致密层）之间急剧下降；(c) 随着时间推移，在系膜区可见葡聚糖蓄积；(d) 在任何时候裂隙处均未见葡聚糖蓄积。这些结果与先前在正常动物中报道的结果相同，表明在肾病患者中，基底膜仍然作为保留大部分血浆蛋白的主要滤过屏障。还注意到与正常情况的某些差异，即基底膜上皮侧存在增加量的示踪剂：(a) 在尿腔中；(b) 在基底膜的上皮下部分；(c) 在肾小管上皮细胞质内的溶酶体（蛋白吸收滴）中。此外，可见基底膜致密部分（致密层）变薄区域，同时伴有较疏松的内皮下层和上皮下层（分别为内疏松层和外疏松层）相应增宽。基底膜上皮侧存在增加量的葡聚糖表明滤器，即基底膜，存在渗漏，允许葡聚糖进而血浆蛋白的通透性增加。
