Grond J, Weening J J, Elema J D
Lab Invest. 1984 Sep;51(3):277-85.
The development of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) and its relation to mesangial accumulation of macromolecular substances, lipids in particular, were studied in two models of the nephrotic syndrome, induced by puromycin aminonucleoside and adriamycin. Rats with chronic nephrosis induced by multiple subcutaneous injections of puromycin aminonucleoside during 12 weeks showed FSGHS lesions in 7.8% of their glomeruli. Only 0.3% of the glomeruli from rats with chronic nephrosis of 12 weeks' duration induced by one intravenous dose of adriamycin showed FSGHS lesions (p = 0.0012). Body weight curves, proteinuria, and serum levels of total protein, cholesterol, and triglycerides were similar in both groups. The mesangial area in glomeruli of puromycin aminonucleoside-nephrotic rats showed significantly higher amounts of lipid as compared with glomeruli in adriamycin-nephrotic rats, and within FSGHS lesions in particular extensive accumulation of lipid was observed. In addition, increased lipid accumulation within the mesangial area was found in rats with acute (i.e., of 10 days' duration) puromycin aminonucleoside nephrosis as compared with rats with acute adriamycin nephrosis. These differences in lipid accumulation between the two models may reflect differences in mesangial cell injury or, more likely, in function. In puromycin aminonucleoside nephrosis the increased mesangial uptake of tracers is well known. Mesangial function in unilateral adriamycin nephrosis was studied using colloidal carbon as a tracer. No differences in mesangial handling of carbon were observed between adriamycin-perfused, contralateral nonperfused, and saline-perfused control kidneys. In chronic puromycin aminonucleoside nephrosis increased accumulation and incorporation of macromolecular substances, such as lipids in mesangial cells, may lead to overproduction of matrix substance with more trapping of lipids and eventually sclerosis. In adriamycin nephrosis normal mesangial activity and, consequently, low uptake of macromolecules and endogenous lipids may protect the glomerulus against sclerosis, notwithstanding increased serum lipid levels.
在嘌呤霉素氨基核苷和阿霉素诱导的两种肾病综合征模型中，研究了局灶节段性肾小球玻璃样变和硬化（FSGHS）的发展及其与系膜中大分子物质（特别是脂质）蓄积的关系。在12周内多次皮下注射嘌呤霉素氨基核苷诱导慢性肾病的大鼠，其肾小球中7.8%出现FSGHS病变。单次静脉注射阿霉素诱导12周慢性肾病的大鼠，仅0.3%的肾小球出现FSGHS病变（p = 0.0012）。两组大鼠的体重曲线、蛋白尿以及总蛋白、胆固醇和甘油三酯的血清水平相似。与阿霉素肾病大鼠的肾小球相比，嘌呤霉素氨基核苷肾病大鼠肾小球的系膜区脂质含量显著更高，尤其是在FSGHS病变内观察到脂质大量蓄积。此外，与急性阿霉素肾病大鼠相比，急性（即病程10天）嘌呤霉素氨基核苷肾病大鼠的系膜区内脂质蓄积增加。两种模型中脂质蓄积的这些差异可能反映了系膜细胞损伤的差异，或者更可能是功能的差异。在嘌呤霉素氨基核苷肾病中，系膜对示踪剂摄取增加是众所周知的。使用胶体碳作为示踪剂研究了单侧阿霉素肾病的系膜功能。在阿霉素灌注的、对侧未灌注的和生理盐水灌注的对照肾脏之间，未观察到系膜对碳的处理存在差异。在慢性嘌呤霉素氨基核苷肾病中，系膜细胞中脂质等大分子物质的蓄积和掺入增加，可能导致基质物质过度产生，更多地捕获脂质并最终导致硬化。在阿霉素肾病中，尽管血清脂质水平升高，但正常的系膜活性以及因此对大分子和内源性脂质的低摄取可能保护肾小球免于硬化。
