Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin.

Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin.
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DOI:
10.1172/jci114816
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发表时间:
1990-10
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
K. Harris;J. Lefkowith;S. Klahr;G. Schreiner
K. Harris;J. Lefkowith;S. Klahr;G. Schreiner
中科院分区:
其他
文献类型:
--
作者:
K. Harris;J. Lefkowith;S. Klahr;G. Schreiner

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给大鼠施用氨基核苷嘌呤霉素 (PAN) 会导致肾病综合征,该综合征与肾功能急性下降和间质浸润有关。我们检查了必需脂肪酸缺乏(EFAD)是否会影响 PAN 引起的肾功能障碍,这种缺乏会抑制肾小球肾炎中的巨噬细胞浸润。对照大鼠和 EFAD 大鼠均出现蛋白尿,并在 28 天内消退。给予 PAN 后,正常饮食的大鼠体内出现明显的巨噬细胞浸润。 EFAD 饮食阻止了渗透。 7天时,缺乏巨噬细胞间质浸润与EFAD大鼠的Cin显着高于对照组相关(5.21+/-1.19对比0.39+/-0.08,P小于0.002ml/min/kg BW)。此外,到第 7 天,对照组的 CPAH 降至低于 10 ml/min/kg BW,但 EFAD 中的 CPAH 仍与正常值相同。对照大鼠给予 PAN 后,尿液中血栓素排泄量或肾小球血栓素产生量均未增加。此外,给予血栓素合酶抑制剂无法模拟 EFAD 的效果。正常饮食的大鼠中辐射引起的白细胞减少症显着改善了急性肾病大鼠的肾小球滤过和肾血流量。 EFAD 可防止间质细胞浸润和与实验性肾病相关的肾缺血。 PAN 后单核细胞募集至肾脏直接导致肾功能下降。
The administration of the aminonucleoside of puromycin (PAN) to rats causes the nephrotic syndrome that is associated with an acute decline in renal function, and an interstitial infiltrate. We examined whether essential fatty acid deficiency (EFAD), which inhibits macrophage infiltration in glomerulonephritis, affects PAN-induced renal dysfunction. Both control and EFAD rats developed proteinuria that resolved over 28 d. After PAN administration, there was a prominent infiltration of macrophages in rats fed a normal diet. The infiltrate was prevented by the EFAD diet. The absence of a macrophage interstitial infiltrate was associated with a significantly higher Cin in the EFAD rats than in controls at 7 d (5.21 +/- 1.19 versus 0.39 +/- 0.08, P less than 0.002 ml/min/kg BW). In addition, CPAH fell to less than 10 ml/min/kg BW by day 7 in controls, but remained the same as normal in the EFAD. After administration of PAN to control rats, there was no increase in urinary thromboxane excretion or an increase in glomerular thromboxane production. Furthermore, the effect of EFAD could not be mimicked by the administration of a thromboxane synthase inhibitor. Irradiation-induced leukopenia in rats on a normal diet markedly improved glomerular filtration and renal blood flow in acutely nephrotic rats. EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. The recruitment of mononuclear cells into the kidney following PAN directly contributes to the decline in renal function.