Tesar V, Zima T, Poledne R, Stejskalová A, Tĕmínová J, Stípek S
I interní klinika, 1. lékarská fakulta Univerzity Karlovy, Praha, Czech Republic.
Sb Lek. 1995;96(1):35-42.
Hyperlipidemia is not only a prominent complication of nephrotic syndrome, but it may also contribute to the further non-immunologic damage of glomeruli. Analogy between atherosclerosis and glomerular sclerosis was suggested. Treatment of hyperlipidemia may decrease proteinuria in nephrotic animals and subjects and possibly prevent the progression of glomerulosclerosis and renal failure. We decided to study the influence of therapy with the inhibitor of cholesterol synthesis, lovastatin, on the development of the experimental nephrotic syndrome induced by the administration of adriamycine in rats.
Nephrotic syndrome was induced in rats by the intravenous administration of adriamycine. One group of animals was treated from the time of adriamycine adminstration with lovastatin. Lovastatin was also given to one group of control animals. Proteinuria increased significantly during 4 weeks in untreated adriamycine rats (from 0.93 + 0.57 to 12.76 + 11.95 g/mmol of urinary creatinine, p < 0.01), but it did not change significantly in adriamycine rats treated with lovastatin (from 0.98 + 0.69 to 1.90 + 4.25 g/mmol of creatinine, p = n.s.) and it was significantly lower than in untreated animals (p < 0.01). Plasma albumin decreased 12 weeks after adriamycine administration in untreated rats (from 21.16 + 1.45 to 10.58 + 3.83 g/l, p < 0.001) significantly more (p < 0.05) than in rats treated with lovastatin (from 20.01 + 2.18 to 15.34 + 2.66 g/l, p < 0.01). Lovastatin also ameliorated the increase of plasma cholesterol and eliminated the increase of plasma triglycerides in adriamycine rats. Metabolic changes were in all groups characterized by the increase of free fatty acids, possibly due to exaggerated lipolysis, but without significant change of glycaemia and plasma urea. Proteinuria was decreasing at the end of the observed period. Histologically there were only minimal changes in glomeruli, without significant glomerulosclerosis.
Administration of lovastatin prevented the development of nephrotic syndrome in experimental adriamycine nephropathy in rats. This finding suggests the possible role of hyperlipidemia in the pathogenesis of glomerular damage and suggests the posibility to prevent glomerulosclerosis and renalisufficiency in some form on nephrotic syndrome by the effective hypolipidemic therapy.
高脂血症不仅是肾病综合征的一个突出并发症，还可能导致肾小球进一步的非免疫性损伤。有人提出动脉粥样硬化与肾小球硬化之间存在相似性。高脂血症的治疗可能会降低肾病动物和患者的蛋白尿，并有可能预防肾小球硬化和肾衰竭的进展。我们决定研究胆固醇合成抑制剂洛伐他汀对大鼠静脉注射阿霉素诱导的实验性肾病综合征发展的影响。
通过静脉注射阿霉素诱导大鼠肾病综合征。一组动物从注射阿霉素时开始用洛伐他汀治疗。另一组对照动物也给予洛伐他汀。未治疗的阿霉素大鼠在4周内蛋白尿显著增加（从0.93±0.57增加到12.76±11.95g/mmol尿肌酐，p<0.01），但用洛伐他汀治疗的阿霉素大鼠蛋白尿没有显著变化（从0.98±0.69增加到1.90±4.25g/mmol肌酐，p=无显著性差异），且显著低于未治疗的动物（p<0.01）。未治疗的大鼠在注射阿霉素12周后血浆白蛋白显著降低（从21.16±1.45降至10.58±3.83g/l，p<0.001），比用洛伐他汀治疗的大鼠降低得更多（p<0.05）（从20.01±2.18降至15.34±2.66g/l，p<0.01）。洛伐他汀还改善了阿霉素大鼠血浆胆固醇的升高并消除了血浆甘油三酯的升高。所有组的代谢变化均以游离脂肪酸增加为特征，这可能是由于脂解作用增强，但血糖和血浆尿素无显著变化。在观察期末蛋白尿减少。组织学上肾小球仅有微小变化，无明显的肾小球硬化。
给予洛伐他汀可预防大鼠实验性阿霉素肾病中肾病综合征的发展。这一发现提示高脂血症在肾小球损伤发病机制中的可能作用，并提示通过有效的降脂治疗有可能以某种形式预防肾病综合征中的肾小球硬化和肾功能不全。
