急性胰腺炎大鼠腎臟中聚腺苷二磷酸核糖聚合酶-1 mRNA的表達及意義_《中國普外基礎與臨床雜志》

作者：

惠遠見 , 王衛星 , 余佳 , 鄧文宏 , 陳曉燕 , 崔周軍 , 阿布力克木阿布力孜

武漢大學人民醫院普通外科(武漢 430060);

關鍵詞：

急性胰腺炎腎損傷聚腺苷二磷酸核糖聚合酶-1 機理

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目的探討聚腺苷二磷酸核糖聚合酶-1（poly ADPribose polymerase-1,PARP-1） mRNA在重癥急性胰腺炎(severe acute pancreatitis，SAP)大鼠腎臟中的表達及意義。
方法 48只Wistar大鼠按隨機數字表法分為SAP組和假手術組(SO)組，分別于造模術后1、3、6及12 h測定血清肌酐，觀察胰腺和腎臟組織病理變化，并以RT-PCR法檢測PARP-1 mRNA在腎臟中的表達水平。
結果 SAP組大鼠術后血清肌酐逐漸升高，于3、6及12 h明顯高于SO組(P lt;0.05)。SAP組大鼠術后胰腺出現腺體破壞、腺泡壞死、出血、炎性細胞浸潤等病理損害，且呈進行性加重； SO組各時相胰腺組織基本正常。SAP組大鼠術后出現腎小管上皮細胞變性、壞死、腎小球瘀血、缺血等改變，并隨時間延長逐漸加重，其損傷程度在3、6及12 h明顯較SO組嚴重(P lt;0.05)。SO組大鼠腎臟組織僅表達少量PARP-1 mRNA，而SAP組大鼠隨病程延長腎臟組織中PARP-1 mRNA表達逐漸增加，自3 h時起明顯高于SO組（P lt;0.01）。
結論在SAP發病過程中，PARP-1 mRNA的表達在腎臟組織中逐漸增加，PARP-1可能參與了SAP相關腎損傷過程。

引用本文： 惠遠見,王衛星,余佳,鄧文宏,陳曉燕,崔周軍,阿布力克木阿布力孜. 急性胰腺炎大鼠腎臟中聚腺苷二磷酸核糖聚合酶-1 mRNA的表達及意義. 中國普外基礎與臨床雜志, 2010, 17(3): 272-274. doi: 復制

1.	莊永敬, 于永揚, 吳桂榮. 烏司他丁對重癥急性胰腺炎大鼠腎臟細胞凋亡及 bcl2 基因表達的影響 [J]. 中國普外基礎與臨床雜志, 2007; 14(6): 656659, 664.
2.	Pupelis G. Renal failure in acute pancreatitis. Timing of dialysis and surgery [J]. Przegl Lek， 2000; 57 Suppl 5: 2931.
3.	Kes P, Vucicevic＇ Z, Ratkovic＇ Gusic＇ I, et al. Acute renal failure complicating severe acute pancreatitis [J]. Ren Fail, 1996; 18(4): 621628.
4.	Szabó G, Bhrle S, Stumpf N, et al. Poly (ADPRibose) polymerase inhibition reduces reperfusion injury after heart transplantation [J]. Circ Res, 2002; 90(1): 100106.
5.	雷文章, 韋靖江, 沈文律, 等. 實驗性壞死性胰腺炎多器官損害與內毒素血癥的關系 [J]. 中華實驗外科雜志, 1995; 12(3): 131132.
6.	Schmidt C, Hcherl K, Schweda F, et al. Regulation of renal sodium transporters during severe inflammation [J]. J Am Soc Nephrol, 2007; 18(4): 10721083.
7.	Kusske AM, Rongione AJ, Reber HA. Cytokines and acute pancreatitis [J]. Gastroenterology, 1996; 110(2): 639642.
8.	Yekebas EF, Strate T, Zolmajd S, et al. Impact of different modalities of continuous venovenous hemofiltration on sepsisinduced alterations in experimental pancreatitis [J]. Kidney Int, 2002; 62(5): 18061818.
9.	Dobosz M, Mionskowska L, Hac S, et al. Heparin improves organ microcirculatory disturbances in caeruleininduced acute pancreatitis in rats [J]. World J Gastroenterol, 2004; 10(17): 25532556.
10.	王云帆, 陳瑞芬. 急性胰腺炎腎臟損害的發生機制 [J]. 首都醫科大學學報, 2004； 25(2): 276278.
11.	Zhang XP, Wang L, Zhou YF. The pathogenic mechanism of severe acute pancreatitis complicated with renal injury: a review of current knowledge [J]. Dig Dis Sci, 2008; 53(2): 297306.
12.	翟文龍, 張水軍, 崔雪艷, 等. 雷公藤內脂醇對大鼠重癥急性胰腺炎合并腎損傷防護作用 [J]. 中華肝膽外科雜志, 2006; 12(2): 138139.
13.	Amé JC, Spenlehauer C, de Murcia G. The PARP superfamily [J]. Bioessays, 2004; 26(8): 882893.
14.	Graziani G, Battaini F, Zhang J. PARP1 inhibition to treat cancer, ischemia, inflammation [J]. Pharmacol Res, 2005; 52(1): 14.
15.	Decker P, Muller S. Modulating poly (ADPribose) polymerase activity: potential for the prevention and therapy of pathogenic situations involving DNA damage and oxidative stress [J]. Curr Pharm Biotechnol, 2002; 3(3): 275283.
16.	Mazzon E, Genovese T, Di Paola R, et al. Effects of 3aminobenzamide, an inhibitor of poly (ADPribose) polymerase, in a mouse model of acute pancreatitis induced by cerulein [J]. Eur J Pharmacol, 2006; 549(13): 149156.
17.	Du L, Zhang X, Han YY, et al. Intramitochondrial poly(ADPribosylation) contributes to NAD+ depletion and cell death induced by oxidative stress [J]. J Biol Chem, 2003; 278(20): 1842618433.
18.	Pandol SJ, Saluja AK, Imrie CW, et al. Acute pancreatitis: bench to the bedside [J]. Gastroenterology, 2007; 133(3): 1056.e11056.e25.
19.	Gukovskaya AS, Pandol SJ. Cell death pathways in pancreatitis and pancreatic cancer [J]. Pancreatology, 2004; 4(6): 567586.
20.	Nakajima H, Nagaso H, Kakui N, et al. Critical role of the automodification of poly (ADPribose) polymerase1 in nuclear factorkappaBdependent gene expression in primary cultured mouse glial cells [J]. J Biol Chem, 2004; 279(41): 4277442786.
21.	Szabó C, Ischiropoulos H, Radi R. Peroxynitrite: biochemistry, pathophysiology and development of therapeutics [J]. Nat Rev Drug Discov, 2007; 6(8): 662680.
22.	Pacher P, Szabo C. Role of the peroxynitritepoly (ADPribose) polymerase pathway in human disease [J]. Am J Pathol, 2008; 173(1): 213.
23.	Mota RA, SánchezBueno F, Saenz L, et al. Inhibition of poly (ADPribose) polymerase attenuates the severity of acute pancreatitis and associated lung injury [J]. Lab Invest, 2005; 85(10): 12501262.
24.	Ku Y, Sharif R, Dhaulakhandi D, et al. Saluja A.Inhibition of poly (ADP ribose) polymerase attenuates the severity of caeruleininduced pancreatitis and associated lung injury by inhibition of NFkB activation [J]. Pancreas, 2003; 27(4): 392.
25.	Hashimoto K, Ethridge RT, Saito H, et al. The PPARgamma ligand, 15dPGJ2, attenuates the severity of ceruleininduced acute pancreatitis [J]. Pancreas, 2003; 27(1): 5866.

1. 莊永敬, 于永揚, 吳桂榮. 烏司他丁對重癥急性胰腺炎大鼠腎臟細胞凋亡及 bcl2 基因表達的影響 [J]. 中國普外基礎與臨床雜志, 2007; 14(6): 656659, 664.
2. Pupelis G. Renal failure in acute pancreatitis. Timing of dialysis and surgery [J]. Przegl Lek， 2000; 57 Suppl 5: 2931.
3. Kes P, Vucicevic＇ Z, Ratkovic＇ Gusic＇ I, et al. Acute renal failure complicating severe acute pancreatitis [J]. Ren Fail, 1996; 18(4): 621628.
4. Szabó G, Bhrle S, Stumpf N, et al. Poly (ADPRibose) polymerase inhibition reduces reperfusion injury after heart transplantation [J]. Circ Res, 2002; 90(1): 100106.
5. 雷文章, 韋靖江, 沈文律, 等. 實驗性壞死性胰腺炎多器官損害與內毒素血癥的關系 [J]. 中華實驗外科雜志, 1995; 12(3): 131132.
6. Schmidt C, Hcherl K, Schweda F, et al. Regulation of renal sodium transporters during severe inflammation [J]. J Am Soc Nephrol, 2007; 18(4): 10721083.
7. Kusske AM, Rongione AJ, Reber HA. Cytokines and acute pancreatitis [J]. Gastroenterology, 1996; 110(2): 639642.
8. Yekebas EF, Strate T, Zolmajd S, et al. Impact of different modalities of continuous venovenous hemofiltration on sepsisinduced alterations in experimental pancreatitis [J]. Kidney Int, 2002; 62(5): 18061818.
9. Dobosz M, Mionskowska L, Hac S, et al. Heparin improves organ microcirculatory disturbances in caeruleininduced acute pancreatitis in rats [J]. World J Gastroenterol, 2004; 10(17): 25532556.
10. 王云帆, 陳瑞芬. 急性胰腺炎腎臟損害的發生機制 [J]. 首都醫科大學學報, 2004； 25(2): 276278.
11. Zhang XP, Wang L, Zhou YF. The pathogenic mechanism of severe acute pancreatitis complicated with renal injury: a review of current knowledge [J]. Dig Dis Sci, 2008; 53(2): 297306.
12. 翟文龍, 張水軍, 崔雪艷, 等. 雷公藤內脂醇對大鼠重癥急性胰腺炎合并腎損傷防護作用 [J]. 中華肝膽外科雜志, 2006; 12(2): 138139.
13. Amé JC, Spenlehauer C, de Murcia G. The PARP superfamily [J]. Bioessays, 2004; 26(8): 882893.
14. Graziani G, Battaini F, Zhang J. PARP1 inhibition to treat cancer, ischemia, inflammation [J]. Pharmacol Res, 2005; 52(1): 14.
15. Decker P, Muller S. Modulating poly (ADPribose) polymerase activity: potential for the prevention and therapy of pathogenic situations involving DNA damage and oxidative stress [J]. Curr Pharm Biotechnol, 2002; 3(3): 275283.
16. Mazzon E, Genovese T, Di Paola R, et al. Effects of 3aminobenzamide, an inhibitor of poly (ADPribose) polymerase, in a mouse model of acute pancreatitis induced by cerulein [J]. Eur J Pharmacol, 2006; 549(13): 149156.
17. Du L, Zhang X, Han YY, et al. Intramitochondrial poly(ADPribosylation) contributes to NAD+ depletion and cell death induced by oxidative stress [J]. J Biol Chem, 2003; 278(20): 1842618433.
18. Pandol SJ, Saluja AK, Imrie CW, et al. Acute pancreatitis: bench to the bedside [J]. Gastroenterology, 2007; 133(3): 1056.e11056.e25.
19. Gukovskaya AS, Pandol SJ. Cell death pathways in pancreatitis and pancreatic cancer [J]. Pancreatology, 2004; 4(6): 567586.
20. Nakajima H, Nagaso H, Kakui N, et al. Critical role of the automodification of poly (ADPribose) polymerase1 in nuclear factorkappaBdependent gene expression in primary cultured mouse glial cells [J]. J Biol Chem, 2004; 279(41): 4277442786.
21. Szabó C, Ischiropoulos H, Radi R. Peroxynitrite: biochemistry, pathophysiology and development of therapeutics [J]. Nat Rev Drug Discov, 2007; 6(8): 662680.
22. Pacher P, Szabo C. Role of the peroxynitritepoly (ADPribose) polymerase pathway in human disease [J]. Am J Pathol, 2008; 173(1): 213.
23. Mota RA, SánchezBueno F, Saenz L, et al. Inhibition of poly (ADPribose) polymerase attenuates the severity of acute pancreatitis and associated lung injury [J]. Lab Invest, 2005; 85(10): 12501262.
24. Ku Y, Sharif R, Dhaulakhandi D, et al. Saluja A.Inhibition of poly (ADP ribose) polymerase attenuates the severity of caeruleininduced pancreatitis and associated lung injury by inhibition of NFkB activation [J]. Pancreas, 2003; 27(4): 392.
25. Hashimoto K, Ethridge RT, Saito H, et al. The PPARgamma ligand, 15dPGJ2, attenuates the severity of ceruleininduced acute pancreatitis [J]. Pancreas, 2003; 27(1): 5866.

《中國普外基礎與臨床雜志》

急性胰腺炎大鼠腎臟中聚腺苷二磷酸核糖聚合酶-1 mRNA的表達及意義

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《中國普外基礎與臨床雜志》

急性胰腺炎大鼠腎臟中聚腺苷二磷酸核糖聚合酶-1 mRNA的表達及意義

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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