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个体发育过程中肾脏代谢与近端小管转运之间的关系。

The relationship between renal metabolism and proximal tubule transport during ontogeny.

作者信息

Barac-Nieto M, Spitzer A

机构信息

Division of Pediatric Nephrology, Albert Einstein College of Medicine, Rose F. Kennedy Center, Bronx, NY 10461.

出版信息

Pediatr Nephrol. 1988 Jul;2(3):356-67. doi: 10.1007/BF00858693.

DOI:10.1007/BF00858693
PMID:3153041
Abstract

The proximal tubules of newborn and adult animals reabsorb a similar fraction of the filtered load of Na+ and H2O (65%-70%). In tubules from adult animals, transcellular, active Na+ reabsorption accounts for one-third of the total, while two-thirds occur passively through the paracellular pathway, driven by hydrostatic and oncotic forces (one-third) and by cell-generated effective osmotic and ionic gradients (one-third). Since two-thirds of the Na+ is reabsorbed passively and does not require energy, the mature proximal tubule has a high Na+/O2 molar ratio (48 Eq of Na+/mol of O2). Measurements of ouabain-sensitive oxygen consumption in suspensions of proximal tubules indicate that in newborn, aerobic metabolism can support about 50% of the net Na+ transport rate compared with the 33% in tubules from adult animals. Independent confirmation of the direct and proportional relationship between active Na+ transport and ouabain-sensitive O2 consumption exists for the adult but not for the newborn. However, measurements of epithelial conductances and of transepithelial hydrostatic and oncotic pressure differences indicate that passive paracellular fluxes can account for the remaining 50% of the proximal Na+ reabsorption in newborn. The high permeability of the proximal tubules of newborn animals to small molecular weight solutes suggests that cell-generated osmotic and ionic transepithelial gradients are minimal in the tubules of newborn animals. Yet in the newborn, the osmolality of the end proximal tubule fluid was found to exceed that in plasma. This indicates that osmotic gradients due to differences in reflection coefficients for preferentially reabsorbed solutes and Cl- do exist across the proximal tubules of the newborn and suggests that these gradients may contribute to Na+ and H2O reabsorption. If this is indeed the case, then the contribution of active and of hydrostatic and oncotic pressure-driven flows to the overall reabsorption of Na+ and fluid has been overestimated. Resolution of this discrepancy requires measurements of the reflection coefficients for HCO3- and Cl- in the proximal tubule of the newborn. The metabolic processes by which energy is supplied to renal proximal cells during development are also incompletely characterized. There is evidence that maturation of aerobic metabolism, Krebs cycle enzymes activity, and of the mitochondrial membrane surface area precede the development of net reabsorptive transport (Na+, H2O, HCO3, glucose). By contrast, maturation of Na(+)-K(+)-ATPase activity at the basolateral cell membrane follows that in reabsorptive transport and does not limit its development.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

新生动物和成年动物的近端小管对滤过的 Na⁺ 和 H₂O 的重吸收比例相似(65%-70%)。在成年动物的小管中,跨细胞的主动 Na⁺ 重吸收占总量的三分之一,而三分之二则通过细胞旁途径被动重吸收,由静水压和胶体渗透压(三分之一)以及细胞产生的有效渗透压和离子梯度(三分之一)驱动。由于三分之二的 Na⁺ 是被动重吸收且不需要能量,成熟的近端小管具有较高的 Na⁺/O₂ 摩尔比(48 当量的 Na⁺/摩尔 O₂)。对近端小管悬浮液中哇巴因敏感的氧消耗的测量表明,与成年动物的小管相比,新生动物的有氧代谢可支持约 50%的净 Na⁺ 转运速率,而成年动物的小管中这一比例为 33%。对于成年动物,存在主动 Na⁺ 转运与哇巴因敏感的 O₂ 消耗之间直接且成比例关系的独立证实,但新生动物则没有。然而,上皮电导以及跨上皮静水压和胶体渗透压差异的测量表明,被动的细胞旁通量可解释新生动物近端 Na⁺ 重吸收的其余 50%。新生动物近端小管对小分子溶质的高通透性表明新生动物小管中细胞产生的渗透压和离子跨上皮梯度最小。然而,在新生动物中,近端小管末端液体的渗透压被发现超过血浆渗透压。这表明在新生动物的近端小管中,由于优先重吸收的溶质和 Cl⁻ 的反射系数差异而产生的渗透梯度确实存在,并表明这些梯度可能有助于 Na⁺ 和 H₂O 的重吸收。如果确实如此,那么主动以及静水压和胶体渗透压驱动的流动对 Na⁺ 和液体总体重吸收的贡献就被高估了。要解决这一差异,需要测量新生动物近端小管中 HCO₃⁻ 和 Cl⁻ 的反射系数。在发育过程中为肾近端细胞提供能量的代谢过程也尚未完全明确。有证据表明,有氧代谢、三羧酸循环酶活性以及线粒体膜表面积的成熟先于净重吸收转运(Na⁺、H₂O、HCO₃、葡萄糖)的发育。相比之下,基底外侧细胞膜上 Na⁺-K⁺-ATP 酶活性的成熟则滞后于重吸收转运,并且并不限制其发育。(摘要截选至 400 字)

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