Role of aquaporin water channels in kidney function studied using transgenic mice

Several aquaporin (AQP) water transporting proteins are expressed in mammalian kidney: AQP1 in plasma membranes of proximal tubule, thin descending limb of Henle, and descending vasa recta; AQP2 in collecting duct luminal membrane; AQP3 and AQP4 in collecting duct basolateral membrane; AQP6 in intercalated cells; and AQP7 in the S3 segment of proximal tubule. To define the role of aquaporins in renal physiology, we have generated and characterized transgenic null mice deficient in AQP1, AQP3, and AQP4, individually and in combinations, as well as AQP2 mutant mice, in which the T126M mutation causing human nephrogenic diabetes insipidus was introduced. AQP1-deficient mice are polyuric and unable to concentrate their urine in response to water deprivation or vasopressin administration. AQP1 deletion greatly reduces osmotic water permeability in proximal tubule, thin descending limb of Henle, and descending vasa recta, resulting in defective proximal tubule fluid absorption and medullary countercurrent exchange. Mice lacking AQP3 have low basolateral membrane water permeability in cortical collecting duct and excrete large quantities of dilute urine. Mice lacking AQP4 have low water permeability in inner medullary collecting duct, but manifest only a mild defect in maximum urinary concentrating ability. These data, taken together with phenotype analyses of brain, lung, and gastrointestinal organs, support the paradigm that aquaporins facilitate rapid near-isosmolar transepithelial fluid absorption/secretion, as well as rapid vectorial water movement driven by osmotic gradients. The renal phenotype data in aquaporin knockout mice suggests the utility of aquaporin blockers as novel aquaretic-diuretic agents. Received: March 19, 2001 / Accepted: March 22, 2001     

Physiological importance of aquaporins: lessons from knockout mice

The phenotype analysis of transgenic mice deficient in specific aquaporin water channels has provided new insights into the role of aquaporins in organ physiology. AQP1-deficient mice are polyuric and are unable to concentrate their urine in response to water deprivation or vasopressin administration. AQP1 deletion reduces osmotic water permeability in the proximal tubule, thin descending limb of Henle and vasa recta, resulting in defective proximal tubule fluid absorption and medullary countercurrent exchange. Mice lacking AQP3, a basolateral membrane water channel expressed mainly in the cortical collecting duct, are remarkably polyuric but are able to generate a partly concentrated urine after water deprivation. In contrast, mice lacking AQP4, a water channel expressed mainly in the inner medullary collecting duct, manifest only a mild defect in maximum urinary concentrating ability. These data, together with phenotype analyses of the brain, lung, salivary gland, and gastrointestinal organs, support the paradigm that aquaporins can facilitate near-isosmolar transepithelial fluid absorption/secretion as well as rapid vectorial water movement driven by osmotic gradients. The phenotype data obtained from aquaporin knockout mice suggest the utility of aquaporin blockers as novel diuretic agents.     

Roles of aquaporins in kidney revealed by transgenic mice

Transgenic mouse models of aquaporin (AQP) deletion and mutation have been instructive in elucidating the role of AQPs in renal physiology. Mice lacking AQP1 are unable to concentrate their urine because of low water permeability in the proximal tubule, thin descending limb of Henle, and outer medullary descending vasa recta, resulting in defective near-isosmolar fluid absorption in the proximal tubule and defective countercurrent multiplication. Mice lacking functional AQP2, AQP3, or AQP4 manifest various degrees of nephrogenic diabetes insipidus resulting from reduced collecting duct water permeability. Mice lacking AQP7 and AQP8 can concentrate their urine fully, although AQP7 null mice manifest an interesting defect in glycerol reabsorption. Two unexpected renal phenotypes of AQP null mice have been discovered recently, including defective proximal tubule cell migration in AQP1 deficiency, and cystic renal disease in AQP11 deficiency. AQPs thus are important in several aspects of the urinary concentrating mechanism and in functions unrelated to tubular fluid transport. The mouse phenotype data suggest the renal AQPs as targets for the development of aquaretics and potentially for therapy of cystic renal disease and acute renal injury.     

Lessons on renal physiology from transgenic mice lacking aquaporin water channels

Several aquaporin-type water channels are expressed in kidney: AQP1 in the proximal tubule, thin descending limb of Henle, and vasa recta; AQP2, AQP3, and AQP4 in the collecting duct; AQP6 in the papilla; and AQP7 in the proximal tubule. AQP2 is the vasopressin-regulated water channel that is important in hereditary and acquired diseases affecting urine-concentrating ability. It has been difficult to establish the roles of the other aquaporins in renal physiology because suitable aquaporin inhibitors are not available. One approach to the problem has been to generate and analyze transgenic knockout mice in which individual aquaporins have been selectively deleted by targeted gene disruption. Phenotype analysis of kidney and extrarenal function in knockout mice has been very informative in defining the role of aquaporins in organ physiology and addressing basic questions regarding the route of transepithelial water transport and the mechanism of near iso-osmolar fluid reabsorption. This article describes new renal physiologic insights revealed by phenotype analysis of aquaporin-knockout mice and the prospects for further basic and clinical developments.     

Dissecting the roles of aquaporins in renal pathophysiology using transgenic mice

Transgenic mice lacking renal aquaporins (AQPs), or containing mutated AQPs, have been useful in confirming anticipated AQP functions in renal physiology and in discovering new functions. Mice lacking AQPs 1-4 manifest defects in urinary concentrating ability to different extents. Mechanistic studies have confirmed the involvement of AQP1 in near-isosmolar fluid absorption in the proximal tubule, and in countercurrent multiplication and exchange mechanisms that produce medullary hypertonicity in the antidiuretic kidney. Deletion of AQPs 2-4 impairs urinary concentrating ability by reduction of transcellular water permeability in the collecting duct. Recently created transgenic mouse models of nephrogenic diabetes insipidus produced by AQP2 gene mutation offer exciting possibilities to test new drug therapies. Several unanticipated AQP functions in kidney have been discovered recently that are unrelated to their role in transcellular water transport. There is evidence for involvement of AQP1 in kidney cell migration after renal injury, of AQP7 in renal glycerol clearance, of AQP11 in prevention of renal cystic disease, and possibly of AQP3 in regulation of collecting duct cell proliferation. Future work in renal AQPs will focus on mechanisms responsible for these non-fluid-transporting functions, and on the development of small-molecule AQP inhibitors for use as aquaretic-type diuretics.     

Physiology and pathophysiology of renal aquaporins

The discovery of aquaporin-1 (AQP1) by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. In the kidney at least 7 aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have shown that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells and AQP8 are present intracellularly at low abundance in proximal tubules and collecting duct principal cells but the physiological function of these 2 channels remain undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. A series of studies have underscored crucial roles of aquaporins for regulation of renal water metabolism and hence body water balance. Moreover it has become clear that dysregulation of aquaporins, and especially AQP2 is critically involved in many water balance disorders. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting is seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy and SIADH both AQP2 expression levels and apical plasma membrane targetting is increased suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.     

Discovery of aquaporins: a breakthrough in research on renal water transport

Several membranes of the kidney are highly water permeable, thereby enabling this organ to retain large quantities of water. Recently, the molecular identification of water channels responsible for this high water permeability has finally been accomplished. At present, four distinct renal water channels have been identified, all members of the family of major intrinsic proteins. Aquaporin 1 (AQP1), aquaporin 2 (AQP2) and the mercury-insensitive water channel (MIWC) are water-selective channel proteins, whereas the fourth, referred to as aquaporin 3 (AQP3), permits transport of urea and glycerol as well. Furthermore, a putative renal water channel (WCH3) has been found. AQP1 is expressed in apical and basolateral membranes of proximal tubules and descending limbs of Henle, AQP2 predominantly in apical membranes of principal and inner medullary collecting duct cells and AQP3 in basolateral membranes of kidney collecting duct cells. MIWC is expressed in the inner medulla of the kidney and has been suggested to be localised in the vasa recta. The human genes encoding AQP1 and AQP2 have been cloned, permitting deduction of their amino acid sequence, prediction of their two-dimensional structure by hydropathy analysis, speculations on their way of functioning and DNA analysis in patients with diseases possibly caused by mutant aquaporins. Mutations in the AQP1 gene were recently detected in clinically normal individuals, a finding which contradicts the presumed vital importance of this protein. Mutations in the AQP2 gene were shown to cause autosomal recessive nephrogenic diabetes insipidus. The renal unresponsiveness to arginine vasopressin, which characterises this disease, is in accordance with the assumption that AQP2 is the effector protein of the renal vasopressin pathway. The influence of amino acid substitutions on the functioning of AQP1 and 2 was demonstrated by in vitro expression studies in oocytes of the toadXenopus laevis. Future research on renal water transport will focus on the search for other aquaporins, structure-function relationship of aquaporins, the development of aquaporin inhibitors and their possible use as diuretics, and further elucidation of the renal vasopressin pathway.     

Aquaporin-4 expression in adult and developing mouse and rat kidney

Aquaporin-4 (AQP4) is a member of the aquaporin water-channel family. AQP4 is expressed primarily in the brain, but it is also present in the collecting duct of the kidney, where it is located in the basolateral plasma membrane of principal cells and inner medullary collecting duct (IMCD) cells. Recent studies in the mouse also have reported the presence of AQP4 in the basolateral membrane of the proximal tubule. The purpose of this study was to establish the pattern of AQP4 expression during kidney development and in the adult kidney of both the mouse and the rat. Kidneys of adult and 3-, 7-, and 15-d-old mice and rats were preserved for immunohistochemistry and processed using a peroxidase pre-embedding technique. In both the mouse and the rat, strong basolateral immunostaining was observed in IMCD cells and principal cells in the medullary collecting duct at all ages examined. Labeling was weaker in the cortical collecting duct and the connecting tubule, and there was no labeling of connecting tubule cells in the mouse. In adult mouse kidney, strong AQP4 immunoreactivity was observed in the S3 segment of the proximal tubule. However, there was little or no labeling in the cortex or around the corticomedullary junction in 3- and 7-d-old mice. Between 7 and 15 d of age, distinct AQP4 immunoreactivity appeared in the S3 segment of the mouse proximal tubule concomitant with the differentiation of this segment of the nephron. Labeling of proximal tubules was never observed in the rat kidney. These results suggest that there are differences in transepithelial water transport between mouse and rat or that additional, not yet identified water channels exist in the rat proximal tubule.     

水通道蛋白在多囊肾病小鼠肾囊泡上皮细胞的表达与调控

目的 探讨水通道蛋白(AQP)在多囊肾病囊泡上皮细胞的表达和调控。 方法 采用免疫荧光染色和Western印迹法分别检测不同亚型的水通道蛋白AQP1、AQP2、AQP3和AQP4在小鼠常染色体隐性遗传病jck多囊肾小鼠肾脏的表达定位和表达调控。 结果 8周龄jck纯合子小鼠的肾脏占体质量的百分率约是同窝野生型小鼠肾脏的4倍,肾脏组织出现多发、大小不一囊泡,囊泡上皮细胞呈扁平状,肾脏间质可见纤维化。jck小鼠血尿素水平为（42.6±6.7） mmol/L,约是野生型小鼠血尿素水平[（8.4±1.9） mmol/L]的5倍（P < 0.01）。免疫荧光定位分析结果表明AQP1 在近曲小管上皮细胞顶膜和基底膜表达,也表达于髓袢降支细段和直小血管降支,肾囊泡上皮细胞未见AQP1表达。AQP2在集合管和肾囊泡上皮细胞顶膜表达,AQP3和AQP4在集合管和囊泡上皮细胞基底膜表达。Western印迹分析结果表明,jck肾脏AQP2、AQP3和AQP4蛋白表达水平与野生型肾脏相似,但AQP1在jck肾脏的表达水平显著低于其在野生型肾脏的表达水平（P < 0.01）。 结论 jck多囊肾小鼠肾囊泡上皮表达AQP2、AQP3和AQP4,提示肾囊泡来源于肾集合管,水通道蛋白可能在肾囊泡生长过程中起重要作用。     

Physiology and pathophysiology of renal aquaporins

The discovery of aquaporin membrane water channels by Agre and coworkers answered a long-standing biophysical question of how water specifically crosses biologic membranes, and provided insight, at the molecular level, into the fundamental physiology of water balance and the pathophysiology of water balance disorders. Of nine aquaporin isoforms, at least six are known to be present in the kidney at distinct sites along the nephron and collecting duct. Aquaporin-1 (AQP1) is extremely abundant in the proximal tubule and descending thin limb, where it appears to provide the chief route for proximal nephron water reabsorption. AQP2 is abundant in the collecting duct principal cells and is the chief target for vasopressin to regulate collecting duct water reabsorption. Acute regulation involves vasopressin-regulated trafficking of AQP2 between an intracellular reservoir and the apical plasma membrane. In addition, AQP2 is involved in chronic/adaptational regulation of body water balance achieved through regulation of AQP2 expression. Importantly, multiple studies have now identified a critical role of AQP2 in several inherited and acquired water balance disorders. This concerns inherited forms of nephrogenic diabetes insipidus and several, much more common acquired types of nephrogenic diabetes insipidus where AQP2 expression and/or targeting are affected. Conversely, AQP2 expression and targeting appear to be increased in some conditions with water retention such as pregnancy and congestive heart failure. AQP3 and AQP4 are basolateral water channels located in the kidney collecting duct, and AQP6 and AQP7 appear to be expressed at lower abundance at several sites including the proximal tubule. This review focuses mainly on the role of AQP2 in water balance regulation and in the pathophysiology of water balance disorders.     

中国实验用小型猪肾小管的发育及各节段标志物的表达

目的:明确解剖和生理上与人非常接近的中国实验用小型猪肾脏发育过程中肾小管的形态学变化和肾小管各节段的特异性标志物。方法:采用高碘酸-希夫(PAS)染色和免疫荧光染色技术,系统观察中国实验用小型猪妊娠28～112d(E28d～E112d)和出生后1d、7d、14d、21d(P1d～21d),共17个不同时间点猪肾小管的发育及肾小管特异性标志物雪莲花凝集素(LTL)、水通道蛋白1(AQP1)、钙结合蛋白(calbindin)-D28k在肾小管不同节段的表达。结果:(1)中国实验用小型猪E28d可见后肾间充质和输尿管芽,即后肾已经开始发育;但这时还没有肾小管。E35d可见不同节段的肾小管,即肾小管已开始发育。从E35d～P14d(E112d仔猪出生),肾皮质均有生肾区存在,即不断有新的肾单位发生;P21d生肾区消失,即不再有新的肾单位产生。(2)①LTL在E28d表达在输尿管芽,E35d开始在近端小管表达,以刷状缘表达最为明显;表达由弱到强,由点状到线状。②AQP1在E28d未见表达,E35d开始表达;AQP1表达在近端小管和髓袢的降支细段,主要表达在细胞膜,尤其在管腔侧的表达更为明显。③Calbindin-D28k在E28d表达在输尿管芽,E35d开始表达在远端小管和集合管;Calbindin-D28k主要表达在细胞质,随着肾小管发育,表达逐渐增强。(3)发现集合管来源于输尿管芽,发源于输尿管芽的集合管从被膜下的生肾区一直延伸到肾髓质。结论:中国实验用小型猪妊娠35d可以见到不同节段肾小管。LTL、AQP1、Calbindin-D28k可以分别作为猪近端小管、髓袢、远端小管和集合管的标志物。     

Aquaporin mediated water flux as a target for diuretic development

Within the past decade an entire family of membrane proteins--aquaporins--which function as transmembrane water channels has been identified; they occur throughout the plant, animal, and bacterial kingdoms. Several family members permit glycerol and urea permeability. Most aquaporins are inhibited by mercury. Constitutively expressed aquaporin 1 is the major permeability channel of the proximal tubule, descending thin limb of the loop of Henle, and it is also found in vasa recta. Aquaporin 2 is expressed in the principal cells of the collecting duct where it shuttles between intracellular vesicles and the apical membrane in response to vasopressin. Aquaporin 2 mutations cause nephrogenic diabetes insipidus; increased aquaporin 2 activity is implicated in the pathophysiology of heart failure, cirrhosis, and nephrotic syndrome. Aquaporins 3 and 4 provide basolateral membrane water channels in the collecting duct. These 4 channels and 6 others are also found elsewhere throughout the body. The physiological importance of several of the channels remains unknown. Aquaporin 1 inhibitors might induce useful diuresis, but humans who lack aquaporin 1 have no significant clinical disease. Inhibition of aquaporin 2 activity by vasopressin receptor antagonists may be useful in heart failure, cirrhosis, nephrotic syndrome, and the syndrome of inappropriate antidiuretic hormone (ADH) release.     

Effect of cortical-medullary gradient for ammonia on urinary excretion of ammonia

Previous studies suggested that a portion of ammonia secreted into the proximal tubule may diffuse directly from Henle's loop into the medullary collecting duct. Since water is absorbed along the course of the descending portion of the loop, it was proposed that the concentration of ammonia increased in loop fluid, and that rapid diffusibility of the free base would facilitate the delivery of ammonia into medullary interstitium where a high level could be maintained by the countercurrent exchange process. In this schema it was proposed that there was an ammonia concentration gradient between medullary structures and cortex, and recovery of ammonia by the medullary collecting duct due to the low pH in tubule fluid at that site. The present study was designed to evaluate this hypothesis by estimating ammonia concentrations in medullary and cortical tissue, and by correlating medullary levels with secretion rate into the inner medullary collecting duct. In control animals the concentration of total ammonia (NH4+ + NH3+) in inner medullary vasa recta was 9.2 +/- 1.5 mumoles/ml, a level 100-fold higher than the cortical level of 0.10 +/- 0.01. During acute acidosis the medullary level rose to 22.5 +/- 2.7 mumoles/ml, but in acute acidosis during mannitol infusion the level fell to 8.0 +/- 1.2. The rate of ammonia secretion into inner medullary collecting duct fluid correlated directly with medullary vasa recta ammonia concentration. These data provide evidence for a steep ammonia concentration gradient between the medulla and cortex, and suggest that the diffusion gradient across collecting duct epithelium governs the rate of the addition of ammonia to collecting duct fluid.     

Angiotensin II stimulates vacuolar H+ -ATPase activity in renal acid-secretory intercalated cells from the outer medullary collecting duct

Final urinary acidification is mediated by the action of vacuolar H(+)-ATPases expressed in acid-secretory type A intercalated cells (A-IC) in the collecting duct. Angiotensin II (AngII) has profound effects on renal acid-base transport in the proximal tubule, distal tubule, and collecting duct. This study investigated the effects on vacuolar H(+)-ATPase activity in A-IC in freshly isolated mouse outer medullary collecting ducts. AngII (10 nM) stimulated concanamycin-sensitive vacuolar H(+)-ATPase activity in A-IC in freshly isolated mouse outer medullary collecting ducts via AT(1) receptors, which were also detected immunohistochemically in A-IC. AngII increased intracellular Ca(2+) levels transiently. Chelation of intracellular Ca(2+) with BAPTA and depletion of endoplasmic reticulum Ca(2+) stores prevented the stimulatory effect on H(+)-ATPase activity. The effect of AngII on H(+)-ATPase activity was abolished by inhibitors of small G proteins and phospholipase C, by blockers of Ca(2+)-dependent and -independent isoforms of protein kinase C and extracellular signal-regulated kinase 1/2. Disruption of the microtubular network and cleavage of cellubrevin attenuated the stimulation. Finally, AngII failed to stimulate residual vacuolar H(+)-ATPase activity in A-IC from mice that were deficient for the B1 subunit of the vacuolar H(+)-ATPase. Thus, AngII presents a potent stimulus for vacuolar H(+)-ATPase activity in outer medullary collecting duct IC and requires trafficking of stimulatory proteins or vacuolar H(+)-ATPases. The B1 subunit is indispensable for the stimulation by AngII, and its importance for stimulation of vacuolar H(+)-ATPase activity may contribute to the inappropriate urinary acidification that is seen in patients who have distal renal tubular acidosis and mutations in this subunit.     

Decreased abundance of collecting duct aquaporins in post-ischemic renal failure in rats.

Increased urine flow is often a feature of mild to moderate acute renal failure. This study examines the possible role of dysregulation of collecting duct aquaporins as a factor in this increase. In rats, the left renal pedicle was clamped for 45 min followed by contralateral nephrectomy. Control rats were identical except that the renal pedicle was not clamped. Rats were sacrificed and the kidneys were homogenized at various time points after release of the clamp for semiquantitative immunoblotting of collecting duct aquaporins, as well as the thick ascending limb Na-K-2Cl cotransporter and the proximal tubule water channel, aquaporin-1. Urinary flow rate was significantly increased 18 h after the ischemic insult and remained increased through 72 h. Whole kidney aquaporin-2 protein abundance was 45% of controls at 18 h, 55% of controls at 36 h, and returned to normal 72 h after ischemia. Whole kidney aquaporin-3 protein abundance was 37% of controls at 18 h, 13% of controls at 36 h, and 45% of controls at 72 h. The decline in aquaporin-2 and -3 was confirmed by immunocytochemistry. Abundance of the thick ascending limb Na-K-2Cl cotransporter protein was not significantly decreased. Aquaporin-1 protein abundance was not significantly decreased at 18 h after the ischemic insult, but was significantly reduced after 36 h. Thus, the post-ischemic state is associated with decreased levels of the collecting duct aquaporins, coinciding with an increase in water excretion. It is concluded that decreased aquaporin protein abundance in collecting duct cells is a contributing factor in the increased urine flow seen in moderate post-ischernic acute renal failure.     

Aquaporin-1 facilitates epithelial cell migration in kidney proximal tubule

Aquaporin-1 (AQP1) is the principal water-transporting protein in cell plasma membranes in kidney proximal tubule, where it facilitates transepithelial water transport. Here, a novel role for AQP1 in kidney involving the migration of proximal tubule cells is reported. Migration was compared in primary cultures of proximal tubule cells from wild-type and AQP1 null mice. Cell cultures from AQP1 null mice were indistinguishable from those of wild-type mice in their appearance, growth/proliferation, and adhesiveness, although, as expected, they had reduced plasma membrane water permeability. Migration of AQP1-deficient cells was reduced by >50% compared with wild-type cells, as measured in a Boyden chamber in the presence of a chemotactic stimulus. Comparable slowing of migration of AQP1-deficient cells was also found in an in vitro scratch assay of wound healing, with reduced appearance of lamella-like membrane protrusions at the cell leading edge. Adenoviral-mediated expression of AQP1 in the AQP1-deficient cells, which increased their water permeability to that of wild-type cells, corrected their migration defect. The potential relevance of these in vitro findings to the intact kidney was tested in an in vivo model of acute tubular injury caused by 30 min of renal artery occlusion. At 3 to 5 d after ischemia-reperfusion, kidneys in AQP1 null mice showed remarkably greater tubular injury and cellular actin disorganization than kidneys in wild-type mice. These results provide evidence for the involvement of AQP1 in migration of proximal tubule cells and possibly in the response of the proximal tubule to injury.     

原发性肾病综合征患者尿水通道蛋白异常及其意义

目的：探讨原发性肾病综合征患者尿液水通道蛋白含量变化与其在肾组织中表达量的相关性.方法：54例经肾活检病理证实为原发性肾小球疾病的患者分为3组,即非NS组（A组）、NS不伴水肿组（B组）、NS伴水肿组（C组）,应用ELISA法检测患者尿液AQP1及AQP2含量,免疫组化法检测3组患者肾组织AQP1及AQP2的表达.结果：（1）C组尿液AQP1含量为（43.078±17.923）μg,较A组的（39.189±12.448）μg及B组的（41.492±14.766）μg有升高,但差异无统计学意义;C组（45.309±16.921）μg、B组（38.621±13.187）μg尿AQP2含量显著高于A组的（30.320±9.528）μg;（2）AQP1主要表达于近端小管,C组AQP1阳性面积百分比为（0.414±0.201）%,显著低于A组的（0.683±0.311）%及B组的（0.652±0.300）%,A、B组间表达差异无统计学意义;AQP2主要表达于集合管,C组AQP2阳性面积百分比为（0.823±0.002）%,显著高于A组的（0.512±0.213）%及B组的（0.665±0.228）%,A、B两组间表达也差异有统计学意义;（3）尿AQP1含量与AQP1阳性面积百分比无显著相关性;B、C两组尿AQP2含量与AQP2阳性面积百分比呈显著正相关.结论：尿AQP2含量能反映其在肾组织中表达的多寡,但尿AQP1含量与其在肾组织的表达无明显相关.