Heyman S N, Rosen S, Epstein F H, Spokes K, Brezis M L
Charles A. Dana Research Institute, Department of Medicine, Harvard Medical School, Boston Massachusetts.
Kidney Int. 1994 Apr;45(4):981-5. doi: 10.1038/ki.1994.132.
The straight portion (S3) of the proximal tubule lies in close proximity to the thick ascending limbs (TALs) at the cortico-medullary junction. Since a delicate balance exists between oxygen demand and the limited oxygen supply in this region, we hypothesized that reduction of thick limb metabolic activity might augment oxygen availability to S3 segments, which depend heavily upon aerobic metabolism, and prevent hypoxic damage. The degree of functional deterioration and morphological damage to S3 was assessed in isolated rat kidneys perfused with an erythrocyte-free medium. Bumetanide (10(-5) M) and furosemide (10(-4) M) reduced S3 fragmentation from 9.8 +/- 3.9% of tubules in controls to 0 and 1.4 +/- 0.9%, respectively (P < 0.0005). Tubular glucose reabsorption was better preserved in kidneys exposed to loop diuretics than in control kidneys (P < 0.01), and urinary alkaline phosphatase (P < 0.05) and the total amount of LDH released into the perfusate and urine (P < 0.01) were lower in the treatment groups. Morphological damage to S3 was closely correlated with medullary TAL necrosis (r = 0.66, P < 0.001), urinary alkaline phosphatase excretion (r = 0.89, P < 0.001) and glycosuria (r = 0.83, P < 0.001). We conclude that under hypoxic conditions TALs and S3 segments may compete with each other for a limited oxygen supply. Reduction of active transport in the mTAL might augment oxygen availability to S3 segments and improve their survival.
近端小管的直部（S3）位于皮质-髓质交界处，紧邻髓袢升支粗段（TALs）。由于该区域的氧需求与有限的氧供应之间存在微妙的平衡，我们推测降低髓袢升支粗段的代谢活性可能会增加对严重依赖有氧代谢的S3节段的氧供应，并预防缺氧损伤。在灌注无红细胞培养基的离体大鼠肾脏中评估S3的功能恶化程度和形态损伤。布美他尼（10⁻⁵ M）和呋塞米（10⁻⁴ M）分别将S3节段的碎片化率从对照组小管的9.8±3.9%降至0和1.4±0.9%（P<0.0005）。与对照组肾脏相比，暴露于袢利尿剂的肾脏中肾小管葡萄糖重吸收得到更好的保留（P<0.01），治疗组的尿碱性磷酸酶（P<0.05）以及释放到灌注液和尿液中的乳酸脱氢酶总量（P<0.01）较低。S3的形态损伤与髓质TAL坏死（r = 0.66，P<0.001）、尿碱性磷酸酶排泄（r = 0.89，P<0.001）和糖尿（r = 0.83，P<0.001）密切相关。我们得出结论，在缺氧条件下，TALs和S3节段可能会相互竞争有限的氧供应。降低髓质TAL中的主动转运可能会增加S3节段的氧供应并改善其存活情况。
