Pedraza-Chaverrí J, Cruz C, Ibarra-Rubio M E, Chávez M T, Calleja C, Tapia E, del Carmen Uribe M, Romero L, Peña J C
Departamento de Nefrología y Metabolismo Mineral, Instituto Nacional de la Nutrición Salvador Zubirán, México, D.F.
Rev Invest Clin. 1990 Jan-Mar;42(1):29-38.
The pathophysiology of the nephrotic syndrome (NS), characterized by protenuria, edema, sodium retention and hyperlipidemia, is not clear. We studied the role of some systemic factors on sodium retention in an experimental model of NS. NS was induced in rats by a single subcutaneous injection of puromycin aminonucleoside (PA) (15 mg/100 g); control animals received vehicle. All rats were kept in metabolic cages for 24 days (3 days before and 21 days after PA-injection). Urine was collected daily. Blood samples were obtained every day until day 10, and then every other day up to the end of the study. The rats showed the following alterations after PA injection: a) a rise in serum angiotensin converting enzyme activity (ACEA) and plasma aldosterone (PAldo) at day 1; b) a rise in urinary aldosterone (UAaldoV), azotemia and sodium retention at day 2; c) massive proteinuria (UProt) and decrease in plasma angiotensinogen concentration (PAC) at day 4; d) increases in plasma renin activity (PRA), plasma renin concentration (PRC) and serum creatinine as well as hypoproteinemia, hypercholesterolemia, hypertriglyceridemia, ascitis and edema at day 5; e) increase in urine volume at day 6. PAldo became normal at day 7; urine sodium (UNaV), PRA and PRC at day 8; UAldoV at day 9; serum urea and ACEA at day 10; urinary volume at day 11; PAC, serum total protein and creatinine at day 12. The edema disappeared at day 11. UProt, hypercholesterolemia and hypertriglyceridemia persisted, though they decreased substantially by the end of the study (day 21). Light microscopy studies revealed normal glomerular morphology, but electron microscopy showed fusion of podocytes before proteinuria. These data suggest that: a) sodium retention was not a consequence of proteinuria or hypoproteinemia; b) sodium retention seems non-related to renin secretion, but may be partially mediated by a fall in glomerular filtration rate or by an increased tubular resabsorption secondary to other factors; c) the increase in PAldo, UAldoV and ACEA are non-related to renin secretion: all occurred before PRA rose; d) water retention, increase in PRA and PRC, hypercholesterolemia and hypertriglyceridemia are secondary to the hypoproteinemia.
以蛋白尿、水肿、钠潴留和高脂血症为特征的肾病综合征（NS）的病理生理学尚不清楚。我们在NS实验模型中研究了一些全身因素对钠潴留的作用。通过单次皮下注射嘌呤霉素氨基核苷（PA）（15mg/100g）诱导大鼠发生NS；对照动物注射赋形剂。所有大鼠置于代谢笼中24天（PA注射前3天和注射后21天）。每天收集尿液。在第10天前每天采集血样，然后每隔一天采集一次直至研究结束。PA注射后大鼠出现以下改变：a）第1天时血清血管紧张素转换酶活性（ACEA）和血浆醛固酮（PAldo）升高；b）第2天时尿醛固酮（UAaldoV）、氮质血症和钠潴留增加；c）第4天时出现大量蛋白尿（UProt）且血浆血管紧张素原浓度（PAC）降低；d）第5天时血浆肾素活性（PRA）、血浆肾素浓度（PRC）和血清肌酐升高以及出现低蛋白血症、高胆固醇血症、高甘油三酯血症、腹水和水肿；e）第6天时尿量增加。PAldo在第7天时恢复正常；尿钠（UNaV）、PRA和PRC在第8天时恢复正常；UAldoV在第9天时恢复正常；血清尿素和ACEA在第10天时恢复正常；尿量在第11天时恢复正常；PAC、血清总蛋白和肌酐在第12天时恢复正常。水肿在第11天时消失。UProt、高胆固醇血症和高甘油三酯血症持续存在，不过在研究结束时（第21天）它们大幅下降。光镜检查显示肾小球形态正常，但电镜检查显示在出现蛋白尿之前足细胞融合。这些数据表明：a）钠潴留不是蛋白尿或低蛋白血症的结果；b）钠潴留似乎与肾素分泌无关，但可能部分由肾小球滤过率下降或继发于其他因素的肾小管重吸收增加介导；c）PAldo、UAldoV和ACEA的升高与肾素分泌无关：所有这些都在PRA升高之前发生；d）水潴留、PRA和PRC升高、高胆固醇血症和高甘油三酯血症继发于低蛋白血症。
