NEONATAL PROXIMAL TUBULAR ACIDIFICATION

成人近曲小管重吸收80%的滤过性碳酸氢盐 动物 负责顶端质子分泌的转运蛋白， 基底外侧碳酸氢盐转运已被表征，并且是有限的 到它们各自的膜上， 运输 酸碱变化可影响近端小管的速率 碳酸氢盐吸收，慢性变化可以产生一种内在的 适应转运活动。 然而，人们对此知之甚少。 酸化机制、转运蛋白活性速率和 调节发育中的近端小管中的酸化。 肾发生仍然发生在36周以前出生的新生儿中 怀孕 这些婴儿经常发生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 只相当于成年人的一小部分 然而，不成熟的 近端小管以最大能力发挥功能，或者如果适应性 运输的扩大是可能的。 肾脏的适应能力 急性和慢性酸碱变化影响机体的能力 来应对和生存这些环境压力。 与增加的 早产儿的存活率，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。 该建议的第一个目的是使用体外微灌注， 细胞内pH值的测量，以检查细胞内的分化是如何进行的。 近端小管从原始肾泡到成熟肾小管 节段影响负责运输的定位和活动 用于酸化。 第二个目的是检查是否有急剧变化， 肾小管周围pH、pCO2和HCO3以及肾小管周围物理变化 体外因子可以调节未成熟近端的酸化 小管 最后，我将考察内在发展速度和 近端肾小管酸化的成熟可以通过施加 环境应激对新生家兔的影响 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.