NEONATAL PROXIMAL TUBULAR ACIDIFICATION

成人近端小管可重吸收80%过滤后的重碳酸盐 动物。负责顶端质子分泌的转运体和 碱侧向重碳酸盐的运输已经被表征，并且是有限的 到它们各自的膜上，以获得有效的载体碳酸氢盐 运输。酸碱变化可影响近端小管的比率 碳酸氢盐的吸收，和慢性变化会产生一种内在的 转运蛋白活动中的适应。然而，人们对此知之甚少 酸化机制、转运蛋白活跃率和 发育中的近端小管的酸化调节。 36周前出生的新生儿仍会发生肾病 怀孕了。这些婴儿通常会出现代谢性和呼吸性酸中毒。 已知未成熟的近端小管运输液体和碳酸氢盐 只有成人的一小部分。然而，目前还不清楚是否不成熟。 近端小管功能达到最大能力，或者如果适应性 运输方面的增强是可能的。肾脏的适应能力 急性和慢性酸碱变化会影响机体的能力 以应对这些环境压力并生存下来。随着客户数量的增加 极早产儿的存活，肾脏的适应能力 对代谢性和呼吸性酸中毒具有重要的临床意义。 这项建议的第一个目标是使用体外微灌流和 细胞内pH的测量以检查细胞的分化 从原始肾小泡到成熟肾小管的近端小管 细分影响负责运输者的本地化和活跃性 用于酸化。第二个目标是检查是否有剧烈的变化 肾小管周围pH、PCO2、HCO3及肾小管周围组织的变化 体外因子可调节未成熟近端的酸化 小管。最后，我将检查内在发展速度和 近端肾小管酸化的成熟可以通过施加 经常影响早产儿的新生兔的环境应激 婴儿。

The proximal tubule reabsorbs 80% of the filtered bicarbonate in adult animals. The transporters responsible for apical proton secretion and basolateral bicarbonate transport have been characterized and are limited to their respective membranes for efficient vectorial bicarbonate transport. Acid-base changes can affect the rate of proximal tubule bicarbonate absorption, and chronic changes can produce an intrinsic adaptation in transporter activity. However, little is known about the mechanisms of acidification, the rate of transporter activity and the regulation of acidification in the developing proximal tubule. Nephrogenesis is still occurring in newborn infants born before 36 weeks gestation. These infants often develop metabolic and respiratory acidosis. It is known that immature proximal tubules transport fluid and bicarbonate at a fraction of the adult rate. However, it is unknown whether immature proximal tubules are functioning at maximal capacity or if an adaptive augmentation in transport is possible. The ability of the kidney to adapt to acute and chronic acid-base changes affects the ability of the organism to respond to and survive these environmental stresses. With the increased survivorship of very premature infants, the ability of the kidney to adapt to metabolic and respiratory acidosis is of great clinical importance. The first aim of this proposal is to use in vitro microperfusion and measurements of intracellular pH to examine how differentiation of the proximal tubule from the primitive renal vesicle to the mature tubular segment affects the localization and activity of transporters responsible for acidification. The second aim is to examine if acute changes in peritubular pH, pCO2 and HCO3 as well as changes in peritubular physical factors in vitro can modulate acidification in the immature proximal tubule. Finally, I will examine if the intrinsic rate of development and maturation of proximal tubular acidification can be altered by imposing environmental stresses on newborn rabbits which frequently affect premature infants.