Oqvist B W, Rippe A, Tencer J, Rippe B
Department of Nephrology, University Hospital of Lund, Sweden.
Nephrol Dial Transplant. 1999 Aug;14(8):1898-903. doi: 10.1093/ndt/14.8.1898.
The nephrotic syndrome is characterized by generalized oedema considered to be due to the fall in serum albumin and to sodium retention. The aim of the present study was to investigate whether a generalized disturbance in vascular integrity contributes to the oedema formation.
We used the PAN-(puromycin aminonucleoside) nephritis model in order to induce the nephrotic syndrome in female Wistar rats. Eight rats were given PAN, 15 mg/100 g body weight, intraperitoneally 10 days prior to the study, whereas 21 rats served as controls. Albumin clearance to tissues was measured using a dual isotope technique. Repeated blood samples as well as samples from various muscles, kidney, liver, lung, heart, abdominal wall and from ascites fluid were taken to determine radioactivity and tissue dry-to-wet weights. Clearance of albumin (Clalb) from plasma to interstitium was calculated from the (linear) increment in 'plasma equivalent tissue albumin space' as a function of time, corrected for intravascular volume and oedema. The plasma and urine concentrations of albumin were determined in a parallel study by single radial diffusion using monospecific rabbit anti-rat antiserum in seven PAN animals and 13 controls.
A marked fall in dry-to-wet weight ratios together with pronounced proteinuria, oedema and ascites were found in the PAN animals. Haematocrit decreased from 45% (32-51) to 30% (28-38) and serum albumin from 22.0 g/l (16.3-25.2) to 4.94 g/l (3.20-6.72) in control and PAN animals, respectively. However, Clalb apparently remained unchanged in the PAN animals in comparison to controls in most tissues examined. Thus, in these in vivo experiments there was no direct evidence of an increased extravasation of albumin in extrarenal tissues.
There was no strong support for the contention that a generalized disturbance of capillary integrity outside the renal vasculature would contribute to the oedema formation in the PAN nephrotic syndrome.
肾病综合征的特征是全身性水肿，被认为是由于血清白蛋白下降和钠潴留所致。本研究的目的是调查血管完整性的全身性紊乱是否导致水肿形成。
我们使用嘌呤霉素氨基核苷（PAN）肾炎模型在雌性Wistar大鼠中诱导肾病综合征。在研究前10天，给8只大鼠腹腔注射15mg/100g体重的PAN，而21只大鼠作为对照。使用双同位素技术测量白蛋白向组织的清除率。采集重复的血液样本以及来自各种肌肉、肾脏、肝脏、肺、心脏、腹壁和腹水的样本，以确定放射性和组织干重与湿重。根据“血浆等效组织白蛋白空间”随时间的（线性）增加计算白蛋白从血浆到间质的清除率（Clalb），并校正血管内容量和水肿。在一项平行研究中，使用单特异性兔抗大鼠抗血清通过单向放射扩散法测定7只PAN动物和13只对照动物的血浆和尿液白蛋白浓度。
在PAN动物中发现干重与湿重比显著下降，同时伴有明显的蛋白尿、水肿和腹水。对照组和PAN动物的血细胞比容分别从45%（32 - 51）降至30%（28 - 38），血清白蛋白从22.0g/l（16.3 - 25.2）降至4.94g/l（3.20 - 6.72）。然而，与对照组相比，在大多数检查的组织中，PAN动物的Clalb明显保持不变。因此，在这些体内实验中，没有直接证据表明肾外组织中白蛋白外渗增加。
没有有力证据支持肾血管系统外毛细血管完整性的全身性紊乱会导致PAN肾病综合征水肿形成这一论点。
