梗阻性黃疸對腎臟水通道蛋白-3表達影響的實驗研究_《中國普外基礎與臨床雜志》

作者：

張德巍 ¹ , 關維雨 ¹ , 劉金鋼 ² , 王勇 ²

1.中國醫科大學附屬第四醫院急診外科（遼寧沈陽110032）;;
2.中國醫科大學附屬盛京醫院肝膽外科（遼寧沈陽110005）;

關鍵詞：

梗阻性黃疸急性腎功能衰竭水通道蛋白-3 大鼠

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目的通過檢測梗阻性黃疸（OJ）時大鼠腎臟水通道蛋白-3（AQP-3）基因及蛋白表達的變化，探討其在早期腎功能損害診斷中的價值。方法將Wistar大鼠40只，隨機分為實驗組（n=20，建立OJ動物模型）和對照組（n=20，假手術組）。于術后7 d和14 d，采用全自動生化分析儀檢測各組大鼠血總膽紅素（TBIL）、直接膽紅素（DBIL）、肌酐（Cr）和尿素氮（BUN）水平，并用Western blotting法和RT-PCR法分別檢測各組大鼠腎臟AQP3蛋白和mRNA的表達水平。結果實驗組大鼠術后14 d血清TBIL和DBIL水平明顯高于術后7 d（P=0.000），且均高于相應時相假手術組（P=0.000），而假手術組內兩時相間比較差異無統計學意義（P=0.154），證實OJ模型建立成功。血Cr水平在2組內不同時相間和相同時相組間比較差異均無統計學意義（P gt;0.05）。實驗組大鼠術后14 d的血BUN水平明顯高于術后7 d以及假手術組術后14 d的水平（P=0.001），而假手術組術后兩時相間的差異無統計學意義（P=0.288）。實驗組大鼠術后7 d 及14 d的AQP-3蛋白表達水平均明顯低于相應時相的假手術組（P=0.033，P=0.000），且術后14 d的水平又明顯低于同組術后7 d水平（P=0.000）; 假手術組大鼠術后兩時相的AQP-3蛋白表達水平間的差異無統計學意義（P=0.059）。實驗組大鼠術后7和14 d的AQP-3 mRNA表達水平明顯高于相應時相的假手術組（P=0.000），而兩組內不同時相間比較，其差異均無統計學意義（P=0.139，P=0.059）。結論OJ合并腎功能損害時大鼠腎臟AQP-3 mRNA及蛋白表達的變化早于血肌酐及尿素氮的變化，其變化的應用有望提高OJ時腎功能損害的早期診斷率。

引用本文： 張德巍,關維雨,劉金鋼,王勇. 梗阻性黃疸對腎臟水通道蛋白-3表達影響的實驗研究. 中國普外基礎與臨床雜志, 2011, 18(11): 1175-1179. doi: 復制

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7.	Ohshiro K, Yaoita E, Yoshida Y, et al. Expression and immunolocalization of AQP6 in intercalated cells of the rat kidney collecting duct [J]. Arch Histol Cytol, 2001, 64(3): 329338.
8.	劉金鋼，王勇，宋軍，等．生長激素對實驗性梗阻性黃疸大鼠內毒素血癥的防治 [J]．中華普通外科雜志， 2001， 16（8）： 493494．.
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10.	Pereira JA, Torregrosa MA, MartínezRódenas F, et al. Increaced cardiac endocrine activity after common bile duct ligation in the rabbit. Atrial endocrine cells in obstructive jaundice [J]. Ann Surg, 1994, 219(1): 7378.
11.	Leung JC, Chan LY, Tsang AW, et al. Differential expression of aquaporins in the kidneys of streptozotocininduced diabetic mice [J]. Nephrology (Carlton), 2005, 10(1): 6372.
12.	Gong H, Wang W, Kwon TH, et al. Reduced renal expression of AQP2, pAQP2 and AQP3 in haemorrhagic shockinduced acute renal failure [J]. Nephrol Dial Transplant, 2003, 18(12): 25512559.
13.	Fernándezllama P, Andrews P, Turner R, et al. Decreased abundance of collecting duct aquaporins in postischemic renal failure in rats [J]. J Am Soc Nephrol, 1999, 10(8): 16581668.
14.	Combet S, Geffroy N, Berthonaud V, et al. Correction of agerelated polyuria by ddavp: molecular analysis of aquaporins and urea transporters [J]. Am J Physiol Renal Physiol, 2003, 284(1): F199F208.
15.	Kim SW, Gresz V, Rojek A, et al. Decreased expression of AQP2 and AQP4 water channels and Na, KATPase in kidney collecting duct in AQP3 null mice [J]. Biol Cell, 2005, 97(10): 765778.
16.	Dibas AI, Mia AJ, Yorio T. Aquaporins (water channels): role in vasopressinactivated water transport [J]. Proc Soc Exp Biol Med, 1998, 219(3): 183199.
17.	Fasshauer M, Klein J, Lossner U, et al. Suppression of aquaporin adipose gene expression by isoproterenol, TNF alpha, and dexamethasone [J]. Horm Metab Res, 2003, 35(4): 222227.
18.	Ge Y, Ahn D, Stricklett PK, et al. Collecting ductspecific knockout of endothelin1 alters vasopressin regulation of urine osmolality [J]. Am J Physiol Renal Physiol, 2005, 288(5): F912F920.
19.	Nejsum LN, Zelenina M, Aperia A, et al. Bidirectional regulation of AQP2 trafficking and recycling:involvement of AQP2S256 phosphorylation [J]. Am J Physiol Renal Physiol, 2005, 288(5): F930F938.
20.	Murer L, Addabbo F, Carmosino M, et al. Selective decrease in urinary aquaporin 2 and increase in prostaglandin E2 excretion is associated with postobstructive polyuria in human congenital hydronephrosis [J]. J Am Soc Nephrol, 2004, 15(10): 27052712.
21.	Devuyst O, Combet S, Cnops Y, et al. Regulation of no synthase isoforms in the peritoneum: implications for ultrafiltration failure in peritoneal dialysis [J]. Nephrol Dial Transplant, 2001, 16(3): 675678.
22.	Papakostas C, Bezirtzoglou E, Pitiakoudis M, et al. Endotoxinemia in the portal and the systemic circulation in obstructive jaundice [J]. Clin Exp Med, 2003, 3(2): 124128.
23.	譚毓銓，李有柱．梗阻性黃疸實驗研究的進展與方向 [J]．中國實用外科雜志， 1996， 16（1）： 4951．.
24.	何宇，李昆，何振平．梗阻性黃疸腎缺血再灌注損害及其機制的研究 [J]．重慶醫學， 2002， 31（12）： 11971200．.
25.	Deen PT, Verdijk MA, Knoers NV, et al. Requirement of human renal water channel aquaporin2 for vasopressindependent concentration of urine [J]. Science, 1994, 264(5155): 9295.

1. Fogarty BJ, Parks RW, Rowlands BJ, et al. Renal dysfunction in obstructive jaundice [J]. Br J Surg, 1995, 82(7): 877884.
2. Ingoldby CJ, Mcpherson DA, Blumgart LH. Endotoxemia in human obstructive jaundice: effect of polymyxin B [J]. Am J Surg, 1984, 147(6): 766771.
3. 張豐深，何振平，段恒春．梗阻性黃疸并發腎功能損害的實驗研究 [J]．第三軍醫大學學報， 2002， 24（9）： 10461047．.
4. Agre P, Preston GM, Smith BL, et al. Aquaporin chip: the archetypal molecular water channel [J]. Am J Physiol, 1993, 265(4 Pt 2): 463476.
5. Agre P, Nielsen S. The aquaporin family of water channels in kidney [J]. Néphrologie, 1996, 17(7): 409415.
6. Nielsen S, Frkiaer J, Marples D, et al. Aquaporins in the kidney: from molecules to medicine [J]. Physiol Rev, 2002, 82(1): 205244.
7. Ohshiro K, Yaoita E, Yoshida Y, et al. Expression and immunolocalization of AQP6 in intercalated cells of the rat kidney collecting duct [J]. Arch Histol Cytol, 2001, 64(3): 329338.
8. 劉金鋼，王勇，宋軍，等．生長激素對實驗性梗阻性黃疸大鼠內毒素血癥的防治 [J]．中華普通外科雜志， 2001， 16（8）： 493494．.
9. Yüceyar S, Gümü瘙塂ta瘙塂 K, Ertürk S, et al. The role of oxygen free radicals in acute renal failure complicating obstructive jaundice: an experimental study [J]. HPB Surg, 1998, 10(6): 387393.
10. Pereira JA, Torregrosa MA, MartínezRódenas F, et al. Increaced cardiac endocrine activity after common bile duct ligation in the rabbit. Atrial endocrine cells in obstructive jaundice [J]. Ann Surg, 1994, 219(1): 7378.
11. Leung JC, Chan LY, Tsang AW, et al. Differential expression of aquaporins in the kidneys of streptozotocininduced diabetic mice [J]. Nephrology (Carlton), 2005, 10(1): 6372.
12. Gong H, Wang W, Kwon TH, et al. Reduced renal expression of AQP2, pAQP2 and AQP3 in haemorrhagic shockinduced acute renal failure [J]. Nephrol Dial Transplant, 2003, 18(12): 25512559.
13. Fernándezllama P, Andrews P, Turner R, et al. Decreased abundance of collecting duct aquaporins in postischemic renal failure in rats [J]. J Am Soc Nephrol, 1999, 10(8): 16581668.
14. Combet S, Geffroy N, Berthonaud V, et al. Correction of agerelated polyuria by ddavp: molecular analysis of aquaporins and urea transporters [J]. Am J Physiol Renal Physiol, 2003, 284(1): F199F208.
15. Kim SW, Gresz V, Rojek A, et al. Decreased expression of AQP2 and AQP4 water channels and Na, KATPase in kidney collecting duct in AQP3 null mice [J]. Biol Cell, 2005, 97(10): 765778.
16. Dibas AI, Mia AJ, Yorio T. Aquaporins (water channels): role in vasopressinactivated water transport [J]. Proc Soc Exp Biol Med, 1998, 219(3): 183199.
17. Fasshauer M, Klein J, Lossner U, et al. Suppression of aquaporin adipose gene expression by isoproterenol, TNF alpha, and dexamethasone [J]. Horm Metab Res, 2003, 35(4): 222227.
18. Ge Y, Ahn D, Stricklett PK, et al. Collecting ductspecific knockout of endothelin1 alters vasopressin regulation of urine osmolality [J]. Am J Physiol Renal Physiol, 2005, 288(5): F912F920.
19. Nejsum LN, Zelenina M, Aperia A, et al. Bidirectional regulation of AQP2 trafficking and recycling:involvement of AQP2S256 phosphorylation [J]. Am J Physiol Renal Physiol, 2005, 288(5): F930F938.
20. Murer L, Addabbo F, Carmosino M, et al. Selective decrease in urinary aquaporin 2 and increase in prostaglandin E2 excretion is associated with postobstructive polyuria in human congenital hydronephrosis [J]. J Am Soc Nephrol, 2004, 15(10): 27052712.
21. Devuyst O, Combet S, Cnops Y, et al. Regulation of no synthase isoforms in the peritoneum: implications for ultrafiltration failure in peritoneal dialysis [J]. Nephrol Dial Transplant, 2001, 16(3): 675678.
22. Papakostas C, Bezirtzoglou E, Pitiakoudis M, et al. Endotoxinemia in the portal and the systemic circulation in obstructive jaundice [J]. Clin Exp Med, 2003, 3(2): 124128.
23. 譚毓銓，李有柱．梗阻性黃疸實驗研究的進展與方向 [J]．中國實用外科雜志， 1996， 16（1）： 4951．.
24. 何宇，李昆，何振平．梗阻性黃疸腎缺血再灌注損害及其機制的研究 [J]．重慶醫學， 2002， 31（12）： 11971200．.
25. Deen PT, Verdijk MA, Knoers NV, et al. Requirement of human renal water channel aquaporin2 for vasopressindependent concentration of urine [J]. Science, 1994, 264(5155): 9295.

《中國普外基礎與臨床雜志》

梗阻性黃疸對腎臟水通道蛋白-3表達影響的實驗研究

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《中國普外基礎與臨床雜志》

梗阻性黃疸對腎臟水通道蛋白-3表達影響的實驗研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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