近端肾小管碳酸氢根重吸收的分子机制及代谢性酸中毒

Bicarbonate reabsorption in proximal renal tubule: molecular mechanisms and metabolic acidosis

肾脏的HCO3-重吸收功能对于维持机体的酸碱平衡具有非常重要的意义,HCO3-重吸收障碍会导致代谢性酸中毒。近端肾小管是HCO3-重吸收最主要的部位,约80%的HCO3-在这里被回收至血液中。经过半个多世纪的研究,人们已经对近端肾小管跨上皮细胞的HCO3-转运过程的分子机制有了比较深入的了解。这个过程涉及到上皮细胞的顶端膜与基底侧膜一系列离子转运体的协同作用。在近端肾小管顶端膜,钠氢交换体NHE3和V型质子泵是介导HCO3-重吸收的两个重要途径。其中NHE3负责约50%,V型质子泵约30%,另外20%由其它途径介导。在基底侧膜,Na+/HCO3-共转运体NBCe1负责将HCO3-转运至组织间隙,完成跨上皮细胞运输过程。在本文中,我们梳理了过去半个世纪关于近端肾小管的HCO3-重吸收分子机制研究的历史脉络,重点阐述了最近十来年相关研究的最新进展,深入讨论近端肾小管上皮细胞中酸碱离子转运体的生理学及病理学作用,并就存在的问题进行探讨与展望。

HCO3- reabsorption in the renal tubules plays a critically important role in maintaining the global acid-base balance. Loss of HCO3 causes metabolic acidosis. Proximal renal tubule is the major site for HCO3- reabsorption, accounting for more than 80% of total HCO3- reabsorption along the nephron. Over the past more than half centuries, tremendous progresses have been made on traderstanding the molecular mechanisms underlying the HCO3- reabsorption in proximal tubules. The transepithelial movement of HCO3 involves the coordinated operation of machineries on both the apical and the basolateral membranes of the epithelial cells. On the apical domain, Na＋-H＋ exchanger NHE3 and the vacuolar H＋-ATPase are two major pathways mediating the apical uptake of HCO3--related species. Taken together, NHE3 and H＋-ATPase are responsible for about 80% of HCO3- reabsorption in the proximal tubule. The remaining 20% is likely mediated by pathways yet to be characterized. On the basolateral membrane, NBCel represents the only major known pathway mediating the extrusion of riCO3- coupled with Na＋ into the interstitial space. In the present article, we provide a historical view about the studies on the mechanisms of HCO3- reabsorption since 1940s. Moreover, we summarize the latest progresses emerging over the past decade in the physiological as well as pathological roles of acid-base transporters underlying the HCO3- reabsorption in proximal tubules.