Li C, Wang W, Kwon T H, Isikay L, Wen J G, Marples D, Djurhuus J C, Stockwell A, Knepper M A, Nielsen S, Frøkiaer J
Institute of Experimental Clinical Research, University of Aarhus, DK-8200 Aarhus N, Denmark.
Am J Physiol Renal Physiol. 2001 Jul;281(1):F163-71. doi: 10.1152/ajprenal.2001.281.1.F163.
Previously, we demonstrated that 24 h of bilateral ureteral obstruction (BUO) and short-term release of BUO was associated with a decrease in the expression of aquaporin-2 (AQP2), polyuria, and a reduced urinary concentrating capacity (10). The purposes of the present study were to examine whether BUO and the long-term release of BUO (BUO-R) for 3, 14, and 30 days were associated with changes in the expression of renal AQP1, AQP2, and AQP3 and whether such changes were associated with parallel changes in urinary output and urinary concentrating capacity. Rats (n = 4-7 in each group) were kept in metabolic cages for measurements of urinary output. Kidneys were removed to determine the expression levels of AQP1, AQP2, and AQP3 by semiquantitative immunoblotting. AQP2 was downregulated after 24 h of BUO (42 +/- 3%). Downregulation of AQP2 persisted 3 (43 +/- 14%; P < 0.01) and 15 days after BUO-R (48 +/- 11%; P < 0.01) but was normalized 30 days after BUO-R. AQP3 showed a similar pattern. Moreover, AQP1 was downregulated in response to BUO (65 +/- 7%) and remained downregulated 3 days after BUO-R (41 +/- 5%), 14 days after BUO-R (57 +/- 8%), and 30 days after BUO-R (59 +/- 5%). BUO-R resulted in a significant polyuria that gradually decreased, although it remained significant at day 30. Urinary concentrating capacity remained significantly impaired when determined 3, 14, and 30 days after BUO-R in response to a 24-h period of thirst (1,712 +/- 270 vs. 2,880 +/- 91 mosmol/kgH2O at day 30, P < 0.05). In conclusion, the expression of AQP1, AQP2, and AQP3 were long-term downregulated after BUO-R, suggesting that dysregulation of aquaporins located at the proximal tubule, thin descending limb of the loop of Henle, and the collecting duct may contribute to the long-term polyuria and impairment of urinary concentrating capacity associated with obstructive nephropathy.
此前，我们证明双侧输尿管梗阻（BUO）24小时及短期解除梗阻与水通道蛋白-2（AQP2）表达降低、多尿以及尿浓缩能力下降有关（10）。本研究的目的是检测BUO及长期解除梗阻（BUO-R）3天、14天和30天是否与肾AQP1、AQP2和AQP3表达的变化有关，以及这些变化是否与尿量和尿浓缩能力的相应变化有关。将大鼠（每组n = 4 - 7）置于代谢笼中测量尿量。取出肾脏，通过半定量免疫印迹法测定AQP1、AQP2和AQP3的表达水平。BUO 24小时后AQP2表达下调（42±3%）。AQP2的下调在BUO-R后3天（43±14%；P < 0.01）和15天（48±11%；P < 0.01）持续存在，但在BUO-R后30天恢复正常。AQP3呈现类似模式。此外，AQP1在BUO后表达下调（65±7%），并在BUO-R后3天（41±5%）、14天（57±8%）和30天（59±5%）持续下调。BUO-R导致显著多尿，尽管在第30天仍显著，但多尿程度逐渐减轻。在BUO-R后3天、14天和30天，经24小时禁水后测定的尿浓缩能力仍显著受损（第30天为1,712±270 vs. 2,880±91 mosmol/kgH₂O，P < 0.05）。总之，BUO-R后AQP1、AQP2和AQP3的表达长期下调，提示位于近端小管、髓袢细降支和集合管的水通道蛋白失调可能导致与梗阻性肾病相关联的长期多尿和尿浓缩能力受损。
