Reyes A A, Lefkowith J, Pippin J, Klahr S
Renal Division, Washington University School of Medicine, St. Louis, Missouri.
Kidney Int. 1992 Jan;41(1):100-6. doi: 10.1038/ki.1992.13.
Leukotrienes are products of the 5-lipooxygenase pathway of arachidonic acid metabolism that possess potent inflammatory properties. We examined the potential role of this pathway in the decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) observed in rats after unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Isolated glomeruli from rats with BUO produced significantly greater amounts of leukotriene B4 (LTB4) than glomeruli from sham-operated rats (SOR; P less than 0.0001). Glomeruli from rats with BUO given MK886, an inhibitor of the 5-lipooxygenase enzyme, or from rats with BUO subjected to both total body irradiation to prevent the leukocyte infiltration of the kidney and also given MK886 prior to obstruction, produced amounts of LTB4 not significantly different from those in glomeruli of SOR. Glomeruli from rats with BUO that had only total body irradiation prior to obstruction produced significantly less LTB4 than glomeruli from untreated BUO rats, but LTB4 production was still significantly greater than in glomeruli from SOR. There were no significant differences in GFR among SOR, SOR given MK886, and SOR subjected to total body irradiation. However, SOR given MK886 had significantly higher ERPF and lower renal vascular resistance (RVR) than SOR not pretreated with the lipooxygenase inhibitor. Rats with BUO given MK886, or subjected to total body irradiation, or both, prior to obstruction had significantly greater GFR and ERPF values and lower RVR than untreated BUO rats. Glomeruli from rats with BUO which were not pretreated had three times the leukocytes of glomeruli from SOR. This leukocyte infiltrate was composed of macrophages (about 55%) and neutrophils (about 45%).(ABSTRACT TRUNCATED AT 250 WORDS)
白三烯是花生四烯酸代谢5-脂氧合酶途径的产物，具有强大的炎症特性。我们研究了该途径在单侧解除持续24小时的双侧输尿管梗阻（BUO）后大鼠肾小球滤过率（GFR）降低和有效肾血浆流量（ERPF）下降中可能发挥的作用。与假手术大鼠（SOR）相比，BUO大鼠分离出的肾小球产生的白三烯B4（LTB4）量显著更多（P小于0.0001）。给予5-脂氧合酶抑制剂MK886的BUO大鼠的肾小球，或在梗阻前接受全身照射以防止白细胞浸润肾脏且也给予MK886的BUO大鼠的肾小球，产生的LTB4量与SOR大鼠的肾小球无显著差异。仅在梗阻前接受全身照射的BUO大鼠的肾小球产生的LTB4比未处理的BUO大鼠的肾小球显著减少，但LTB4产量仍显著高于SOR大鼠的肾小球。SOR、给予MK886的SOR和接受全身照射的SOR之间的GFR无显著差异。然而，给予MK886的SOR的ERPF显著更高，肾血管阻力（RVR）更低，比未用脂氧合酶抑制剂预处理的SOR。在梗阻前给予MK886、或接受全身照射、或两者都有的BUO大鼠，其GFR和ERPF值显著高于未处理的BUO大鼠，RVR更低。未预处理的BUO大鼠的肾小球白细胞数量是SOR大鼠肾小球的三倍。这种白细胞浸润由巨噬细胞（约55%）和中性粒细胞（约45%）组成。（摘要截短于250字）
