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[低蛋白饮食及某些药物制剂对大鼠消融性肾病病程的影响]

[The effect of a low-protein diet and certain pharmaceutical agents on the course of ablation nephropathy in rats].

作者信息

Heller J, Cervenka L, Hellerová S

机构信息

Pracovistĕ experimentální medicíny Institutu klinické a experimentální medicíny, Praha.

出版信息

Cas Lek Cesk. 1994 Jul 18;133(14):429-33.

PMID:8069900
Abstract

BACKGROUND

The beneficial effect of a low-protein diet on the course of renal failure after ablation nephropathy in the rat is known; also calcium channel antagonists (CaA) and angiotensin I converting enzyme inhibitors (ACEI) have a protective effect. Because even simple energy restriction retards the development of spontaneous or ablation-induced glomerulosclerosis the authors decided to replace the lacking dietary protein in the low protein diet by starch (disaccharide) and by fat (cereal oil) and compare these two low-protein diets as to their effect on the development of chronic renal failure (CRI) caused by surgical removal of 5/6 of renal parenchyma (5/6 NX).

METHODS AND RESULTS

In Wistar rats just after weaning, 5/6 of renal parenchyma were removed surgically. Thereafter, the rats were fed either a "high-protein" (21%) or two types of a "low-protein" (6%) diet, in one of the latter, the lack of protein was substituted by saccharide, in the other by fat making the substitution "isocaloric" in either case. In all three diet groups, subgroups drinking either tap water or water containing either the ACE-inhibitor enalapril (ena) or the calcium antagonist diltiazem (dil) or both (ena+dil) were formed. On the high-protein diet, an increase in the weight of kidney remnants, in proteinuria and in systolic blood pressure (SBP) was seen. This was prevented by feeding either type of the low-protein diet but also by ena and ena+dil. Ena and ena+dil not only prevented the increase in SBP but actually lowered it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and proteinuria. No additive protective action of ena+dil or ena+low-protein or ena+dil+low-protein was seen suggesting that the lower limit of these protective actions was reached by the low-protein diet alone. There was no substantial difference between either type of low-protein diet except a small and transient decrease in body weight in the first week on a fat-rich diet.

CONCLUSIONS

In the described experiments and with the set-up used the low-protein diet had no effect on the plasma creatinine and urea levels nor on creatinine clearance. The weight of the kidney remnants and proteinuria were significantly higher in animals on a high-protein diet who drank water or water with diltiazem. These changes were suppressed by administration of angiotensin converting enzyme inhibitors either alone or combined with diltiazem. A low- protein diet (both types tested) as well as angiotensin converting enzyme inhibitors improve the course of chronic renal failure in ablation nephropathy in the rat; the authors did not prove an additive effect of the combination of this diet with angiotensin converting enzyme inhibitors.

摘要

背景

低蛋白饮食对大鼠肾切除术后肾衰竭进程的有益作用已为人所知;钙通道拮抗剂(CaA)和血管紧张素I转换酶抑制剂(ACEI)也具有保护作用。由于即使是简单的能量限制也会延缓自发性或切除诱导的肾小球硬化的发展,因此作者决定用淀粉(二糖)和脂肪(谷物油)替代低蛋白饮食中缺乏的膳食蛋白质,并比较这两种低蛋白饮食对手术切除5/6肾实质(5/6 NX)所致慢性肾衰竭(CRI)发展的影响。

方法与结果

在Wistar大鼠刚断奶后,手术切除5/6肾实质。此后,给大鼠喂食“高蛋白”(21%)或两种“低蛋白”(6%)饮食,在后者中的一种,蛋白质缺乏由糖类替代,另一种由脂肪替代,两种替代在任何一种情况下都是“等热量的”。在所有三个饮食组中,形成了分别饮用自来水或含有ACE抑制剂依那普利(ena)或钙拮抗剂地尔硫䓬(dil)或两者(ena + dil)的水的亚组。在高蛋白饮食组中,观察到肾残余重量、蛋白尿和收缩压(SBP)增加。喂食任何一种低蛋白饮食均可预防这种情况,使用ena和ena + dil也可预防。Ena和ena + dil不仅预防了SBP的升高,实际上还使其显著降低。单独使用dil也有降低SBP的作用,但不能预防肾肥大和蛋白尿。未观察到ena + dil或ena + 低蛋白或ena + dil + 低蛋白的附加保护作用,表明仅低蛋白饮食就达到了这些保护作用的下限。除了在富含脂肪的饮食的第一周体重有轻微且短暂的下降外,两种低蛋白饮食之间没有实质性差异。

结论

在所描述的实验和所采用的设置中,低蛋白饮食对血浆肌酐和尿素水平以及肌酐清除率没有影响。饮用自来水或含地尔硫䓬的水的高蛋白饮食动物的肾残余重量和蛋白尿显著更高。单独或与地尔硫䓬联合使用血管紧张素转换酶抑制剂可抑制这些变化。低蛋白饮食(所测试的两种类型)以及血管紧张素转换酶抑制剂可改善大鼠肾切除术后慢性肾衰竭的进程;作者未证明这种饮食与血管紧张素转换酶抑制剂联合使用的附加作用。

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