Kim Hye-Young, Baylis Chris, Verlander Jill W, Han Ki-Hwan, Reungjui Sirirat, Handlogten Mary E, Weiner I David
Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, Gainesville, Florida, USA.
Am J Physiol Renal Physiol. 2007 Oct;293(4):F1238-47. doi: 10.1152/ajprenal.00151.2007. Epub 2007 Jul 25.
Kidneys can maintain acid-base homeostasis, despite reduced renal mass, through adaptive changes in net acid excretion, of which ammonia excretion is the predominant component. The present study examines whether these adaptations are associated with changes in the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). We used normal Sprague-Dawley rats and a 5/6 ablation-infarction model of reduced renal mass; control rats underwent sham operation. After 1 wk, glomerular filtration rate, assessed as creatinine clearance, was decreased, serum bicarbonate was slightly increased, and Na(+) and K(+) were unchanged. Total urinary ammonia excretion was unchanged, but urinary ammonia adjusted for creatinine clearance, an index of per nephron ammonia metabolism, increased significantly. Although reduced renal mass did not alter total Rhcg protein expression, both light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated hypertrophy of both intercalated cells and principal cells in the cortical and outer medullary collecting duct that was associated with increased apical and basolateral Rhcg polarization. Rhbg expression, analyzed using immunoblot analysis, immunohistochemistry, and measurement of cell-specific expression, was unchanged. We conclude that altered subcellular localization of Rhcg contributes to adaptive changes in single-nephron ammonia metabolism and maintenance of acid-base homeostasis in response to reduced renal mass.
尽管肾质量减少，但肾脏可通过净酸排泄的适应性变化来维持酸碱平衡，其中氨排泄是主要组成部分。本研究探讨这些适应性变化是否与氨转运蛋白家族成员Rh B糖蛋白（Rhbg）和Rh C糖蛋白（Rhcg）的变化有关。我们使用正常的Sprague-Dawley大鼠和肾质量减少的5/6切除梗死模型；对照大鼠接受假手术。1周后，以肌酐清除率评估的肾小球滤过率降低，血清碳酸氢盐略有升高，而钠（Na⁺）和钾（K⁺）不变。尿氨总排泄量不变，但经肌酐清除率校正的尿氨（单个肾单位氨代谢的指标）显著增加。虽然肾质量减少未改变Rhcg总蛋白表达，但光学显微镜检查和免疫组织化学结合定量形态分析显示，皮质和外髓集合管中的闰细胞和主细胞均肥大，这与顶端和基底外侧Rhcg极化增加有关。使用免疫印迹分析、免疫组织化学和细胞特异性表达测量分析的Rhbg表达未改变。我们得出结论，Rhcg亚细胞定位的改变有助于单个肾单位氨代谢的适应性变化以及对肾质量减少的酸碱平衡维持。
