Neugarten J, Kozin A, Cook K
Department of Medicine, Montefiore Medical Center, Bronx, New York.
Kidney Int. 1989 Jul;36(1):51-6. doi: 10.1038/ki.1989.160.
The present study was undertaken to determine the effects of prostaglandin synthesis inhibition on glomerular hemodynamics in nephrotoxic serum nephritis and to elucidate the mechanisms by which prostaglandin synthesis inhibition reduces proteinuria in nephritic rats. Dextran sieving studies were performed before and after intravenous administration of indomethacin to control rats and to nephritic rats with heavy proteinuria. Indomethacin did not significantly alter mean arterial pressure, glomerular filtration rate or proteinuria in control rats nor were significant changes in dextran sieving observed. By contrast, in nephritic rats indomethacin significantly reduced glomerular filtration rate (2.58 +/- 0.50 vs. 1.39 +/- 0.27 ml/min, P less than 0.001), proteinuria (0.198 +/- 0.079 vs. 0.048 +/- 0.019 mg/min, P less than 0.05) and filtration rate-corrected proteinuria (0.059 +/- 0.033 vs. 0.031 +/- 0.013 mg/ml GFR, P less than 0.05). The fractional clearance of neutral dextrans with molecular radii exceeding 42 A were elevated above control values in nephritic rats (P less than 0.05). After administration of indomethacin, the fractional clearance of neutral dextrans uniformly declined toward control values and remained elevated only for molecular radii exceeding 54 A. Assessment of glomerular hemodynamics in nephritic rats before and after indomethacin showed significant declines in single nephron filtration rate (31.5 +/- 3.0 vs. 21.2 +/- 2.5 nl/min, P less than 0.02), glomerular plasma flow rate (99.5 +/- 6.7 vs. 68.5 +/- 7.8 nl/min, P less than 0.05) and glomerular ultrafiltration coefficient (0.0430 +/- 0.0033 vs. 0.0339 +/- 0.0032 nl.sec-1.mm Hg-1, p less than 0.05). Indomethacin did not significantly change these parameters in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在确定前列腺素合成抑制对肾毒性血清性肾炎肾小球血流动力学的影响，并阐明前列腺素合成抑制降低肾炎大鼠蛋白尿的机制。在给对照大鼠和重度蛋白尿的肾炎大鼠静脉注射消炎痛前后，进行了右旋糖酐筛分研究。消炎痛未显著改变对照大鼠的平均动脉压、肾小球滤过率或蛋白尿，也未观察到右旋糖酐筛分有显著变化。相比之下，在肾炎大鼠中，消炎痛显著降低了肾小球滤过率（2.58±0.50对1.39±0.27ml/min，P＜0.001）、蛋白尿（0.198±0.079对0.048±0.019mg/min，P＜0.05）和滤过率校正蛋白尿（0.059±0.033对0.031±0.013mg/ml GFR，P＜0.05）。分子半径超过42 Å的中性右旋糖酐的分数清除率在肾炎大鼠中高于对照值（P＜0.05）。注射消炎痛后，中性右旋糖酐的分数清除率均朝着对照值下降，仅分子半径超过54 Å时仍保持升高。对消炎痛前后肾炎大鼠肾小球血流动力学的评估显示，单肾单位滤过率（31.5±3.0对21.2±2.5nl/min，P＜0.02）、肾小球血浆流速（99.5±6.7对68.5±7.8nl/min，P＜0.05）和肾小球超滤系数（0.0430±0.0033对0.0339±0.0032nl·sec-1·mmHg-1，P＜0.05）显著下降。消炎痛未显著改变对照大鼠的这些参数。（摘要截短于250字）
