目的：探讨先天性肾积水患儿肾脏水通道蛋白AQP1-4 的表达与肾实质厚度和肾小球滤过率（GFR）变化之间的关系。方法：利用Western blot检测AQP1-4蛋白在10例先天性肾积水患儿(年龄62.3±18.3个月)10个肾组织和6例来自肾母细胞瘤手术切除患儿的正常肾脏组织(年龄62.7±17.1个月)中的相对表达量。同时对患侧肾脏肾实质厚度和GFR进行评估。积水肾脏AQP1-4表达与GFR以及肾实质厚度之间进行Pearson相关分析检验。结果：肾积水组AQP1-4蛋白相对表达均明显低于正常组（P＜0.05）。B超测量术前积水侧肾脏肾实质厚度平均为4.59±2.25 mm。99mTc-DTPA 测定积水侧肾脏GFR较对侧肾脏明显下降（40±12 mL/min vs 105±20 mL/min, P＜0.05）。积水组肾脏中AQP1-4蛋白相对表达量与肾实质厚度之间呈正相关，与患侧肾脏GFR之间亦呈正相关。积水侧肾脏肾实质厚度与GFR之间呈正相关。结论：先天性积水患儿肾脏AQP1-4蛋白表达下降，其表达量与肾实质厚度和肾脏GFR的变化呈正相关。
Abstract
OBJECTIVE: To study the relationship of renal aquaporin -1, -2, -3, and -4 (AQP1-4) expression with renal parenchymal thickness and glomerular filtration rate (GFR) in children with congenital hydronephrotis. METHODS: Renal tissue samples were obtained from 10 kidneys of 10 children (age: 62.3±18.3 months) with hydronephrosis and who underwent Anderson-Hynes pyeloplasty. Renal control samples were obtained from 6 children (age: 62.7±17.1 months) undergoing nephrectomy for nephroblastoma and were confirmed histologically as normal renal tissues. Renal parenchymal thickness of the hydronephrotic kidneys was measured by ultrasound preoperatively and was verified at operation. Renal GFR was assessed using 99mTc-DTPA scintigraphy preoperatively. Western blot was used to examine the expression of AQP1-4 in the renal tissues. The correlations of renal AQP1-4 expression with the renal parenchymal thickness and GFR were assessed by Pearson correlation analysis. RESULTS: The expression of AQP1-4 in the hydronephrotis group was markedly reduced compared to that in the control group (P<0.05). The mean renal parenchymal thickness of the hydronephrotic kidney was 4.59±2.25 mm measured by ultrasound preoperatively. The mean GFR of the obstructed kidney was significantly lower than that of the contralateral kidney in the hydronephrosis group (40±12 mL/min vs 105±20 mL/min; P<0.05). The expression of AQP1, 2, 3 and 4 was positively correlated with preoperative renal GFR and renal parenchymal thickness in the hydronephrosis group (P<0.05). Renal parenchymal thickness was positively correlated with renal GFR (P<0.05). CONCLUSIONS: The expression of renal AQP1-4 is reduced in children with congenital hydronephrosis. The expression levels of AQP1-4 are positively correlated with renal parenchymal thickness and GFR.
关键词
水通道蛋白 /
先天性肾积水 /
肾实质厚度 /
肾小球滤过率 /
儿童
Key words
Aquaporin /
Congenital hydronephrosis /
Renal parenchymal thickness /
Glomerular filtration rate /
Child
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
［1］Callen PW. Ultrasonography in obstetric and gynecology［M］. 4th ed. Philadelphia: W.B. Saunders Company, 2000: 7.
［2］文建国.新生鼠输尿管不全梗阻后肾盂压力和肾脏形态变化的观察［J］.中华小儿外科杂志， 2002，23（4）：344-347.
［3］文建国，王贵宪，李真珍.幼鼠双侧输尿管梗阻24h后肾脏水通道蛋白1-4的变化［J］.中华小儿外科杂志，2007，28（10）：545-549.
［4］Li C, Wang W, Knepper MA, Nielsen S, Fr-kiaer J. Downregulation of renal aquaporins in response to unilateral ureteral obstruction［J］. Am J Physiol Renal Physiol, 2003, 284(5): F1066-F1069.
［5］Li C, Wang W, Kwon TH, Isikay L, Wen JG, Marples D, et al. Downregulation of AQP1, -2, and-3 after ureteral obstruction is associated with a long-term urine-concentrating defect［J］. Am J Physiol Renal Physiol, 2001, 281(1): F163-F171.
［6］李真珍，文建国，张红，李文才，王焱，杨珂.轻度肾积水儿童肾脏水通道蛋白2、3和4的表达［J］.实用儿科临床杂志，2007，22（22）：1751-1752.
［7］文建国，王炎，李真珍，张国贤，王庆伟，杨黎，等.先天性肾积水肾脏及其尿液中水通道蛋白2表达的相关性研究［J］.中华小儿外科杂志，2009，30（2）：86-90.
［8］文建国，李真珍，范应中，张谦，张红，张国贤，等.先天性积水肾脏组织中水通道蛋白1-4 mRNA表达与肾实质厚度变化的相关性研究［J］.中华泌尿外科杂志，2009，30（4）：1417.
［9］Bobrik II, Dugan IV. The anatomy of human kidneys in ultrasonic study［J］. Vrach Delo, 1991,(5): 73-76.
［10］McDill BW, Li SZ, Kovach PA, Ding L, Chen F. Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation［J］. Proc Natl Acad Sci U S A, 2006, 103(18): 6952-6957.
［11］林善锬.肾素、血管紧张素（RA）系统与临床［J］.中华肾脏病杂志，1989，5（4）：228.
［12］Thornhill BA, Burt LE, Chen C, Forbes MS, Chevalier RL. Variable chronic partial ureteral obstruction in the neonatal rat: a new model of ureteropelvic junction obstruction［J］. Kidney Int, 2005, 67(1): 4252.
［13］Huang WY, Peters CA, Zurakowski D, Borer JG, Diamond DA, Bauer SB, et al. Renal biopsy in congenital ureteropelvic junction obstruction: evidence for parenchymal maldevelopment［J］. Kidney Int, 2006, 69(1): 137-143.
［14］肖永志，周启昌，章鸣，彭清海，范平，云正芬，等.产前超声诊断胎儿泌尿系统发育不良的临床价值［J］.中国当代儿科杂志，2009，7（11）：593-595.
［15］文建国，周玉清，文兰田.B超测定正常儿童肾脏大小和形态［J］.河南医学研究，1995，4（2）：168-171.
［16］Perrome RD. Means of clinical evaluation of renal disease progression［J］. Kidney Int Suppl, 1992, 36: S26-S32.
［17］郑向红，宋厂义，王社教，刘清娥.肾动态显像在小儿先天性肾积水中的临床应用［J］.中国临床医学影像杂志，2000，11（6）：418-420.
［18］姜立新，郭宗远，吴荣德，于启海，刘占峰. 99mTc-DTPA肾动态显像评价新生儿肾积水肾功能［J］.中华核医学杂志，2004，24（2）：110-112.
［19］Shi Y, Li C, Thomsen K, J-rgensen TM, Knepper MA, Nielsen S, et al. Neonatal ureteral obstruction alters expression of renal sodium transporters and aquaporin water channels［J］. Kidney Int, 2004, 66(1): 203-215.
［20］Zhang PL, Peters CA, Rosen S. Ureteropelvic junction obstruction: morphological and clinical studies［J］. Pediatr Nephrol, 2000, 14(8-9): 820-826.
PDF(1006 KB)
