Effect of Urokinase on Severity Acute Pancreatitis with Renal Injury in Rat_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SHI Jingfeng ,  LIU Jingang , GENG Donghua , ZHAO Haiying , YANG Fuquan , YU Yun

Department of Biliary， Bariatric， and Hernia Surgery， Affiliated Shengjing Hospital of China Medical University， Shenyang 110004， Liaoning Province， China;

Corresponding author：

LIU Jingang, Email: liujg51347@hotmail.com

Keywords：

Urokinase; Severity acute pancreatitis; Renal injury; Microcirculation dysfunction

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Objective 　To explore the effect of renal microcirculation following severity acute pancreatitis （SAP） on renal injury and to explore the protection effect of urokinase on them.
Methods 　A total of 192 Wistar rats were randomized divided into normal control group， SAP group， and urokinase group， then rats of 3 groups were sub-divided into 2， 6， 12， and 24 hours group， each group enrolled 16 rats. Of the 16 rats in each subgroup， 8 rats underwent blood flow of renal test， other 8 rats were sacrificed to get blood samples and to perform histopathological examination. The rat models of SAP were established by retrograde injecting with 5% sodium taurocholate into the cholangiopancreatic duct. Radioactive biomicrosphere technique was used to measure the blood flow of renal， levels of plasma thromboxane B2（TXB2） and 6-keto-prostaglandin F1α （6-Keto-PGF1α） were tested by the TXB2 kit and 6-Keto-PGF1α kit， and histopa-thological changes of renal tissues were observed by using HE staining.
Results 　Compared with normal control group at the same time point， the blood flow of renal were lower （P＜0.05）， activity ratio of TXB2 to 6-Keto-PGF1α were higher（P＜0.01）， and the histopathological injury were worse （P＜0.01） in rats of SAP group and urokinase group. Compared with SAP group， the blood flow of renal at 2， 6， and 12 hours in urokinase group were higher （P＜0.01）， the activity ratios of TXB2 to 6-Keto-PGF1α were lower （P＜0.01）， and the histopathological injury were lighter （P＜0.05） in all the 4 time points of urokinase group.
Conclusions 　The renal microcirculation dysfunction and increase of activity ratio of TXB2 to 6-Keto-PGF1α may play an important role in renal injury following SAP in early stage. Urokinase can protect the renal from such injuries.

Citation： SHI Jingfeng,LIU Jingang,GENG Donghua,ZHAO Haiying,YANG Fuquan,YU Yun. Effect of Urokinase on Severity Acute Pancreatitis with Renal Injury in Rat. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(7): 746-751. doi: Copy

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2.	Pezzilli R， Billi P， Morselli-Labate AM. Severity of acute pancr-eatitis：relationship with etiology， sex and age[J]. Hepatogastroenterology， 1998， 45(23)：1859-1864.
3.	Mock BH， Wellman HN. Stoichiometric 99Tcm RBC labeling using stable kit solutions of stannous chloride and EDTA：concise communication[J]. J Nucl Med， 1984， 25(8)：881-886.
4.	王春友，赵玉沛. 重视重症急性胰腺炎多学科综合治疗[J]. 中国实用外科杂志， 2012， 32(7)：517-519.
5.	Raraty MG， Connor S， Criddle DN， et al. Acute pancreatitis and organ failure：pathophysiology， natural history， and management strategies[J]. Curr Gastroenterol Rep， 2004， 6(2)：99-103.
6.	Sha H， Ma Q， Jha RK. Trypsin is the culprit of multiple organ injury with severe acute pancreatitis[J]. Med Hypotheses， 2009， 72(2)：180-182.
7.	李文，郑芳，张集圣. 大承气汤对急性细菌性腹膜炎家兔重要脏器血流的影响[J]. 中国中西医结合外科杂志， 1999， 5(2)：114-116.
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9.	Uhlmann D. Microcirculatory disturbances in the pathogenesis ofacute pancreatitis. //Rodrigo L ed. Acute Pancreatitis[M]. Printedin Croatia， Pubiished by Intechweb. org. December 2011， 141-170.
10.	Parmar MS. Pancreatic necrosis associated with preeclampsia-eclampsia[J]. JOP， 2004， 5(2)：101-104.
11.	崔培林，修瑞娟. 微循环障碍与急性胰腺炎[J]. 世界华人消化杂志， 2004， 12(12)：2853-2855.
12.	Strate T， Mann O， Kleinhans H， et al. Systemic intravenous infusion of bovine hemoglobin significantly reduces microcirculatorydysfunction in experimentally induced pancreatitis in the rat[J]. Ann Surg， 2003， 238(5)：765-771.
13.	Foitzik T， Eibl G， Hotz B， et al. Persistent multiple organ micro-circulatory disorders in severe acute pancreatitis：experimental findings and clinical implications[J]. Dig Dis Sci， 2002， 47(1)：130-138.
14.	Menger MD， Bonkhoff H， Vollmar B， et al. Ischemia-reperfusion-induced pancreatic microvascular injury[J]. Dig Dis Sci， 1996， 41(5)：823-830.
15.	Pelichovská M， Cvachovec K， Hoch J. Intensive care for patientswith severe acute pancreatitis with a significant multiorgan dysfu-nction[J]. Rozhl Chir， 2004， 83(9)：443-450.
16.	Greenstein RJ， Krakoff LR， Felton K. Activation of the renin system in acute pancreatitis[J]. Am J Med， 1987， 82(3)：401-404.
17.	Forgács B， Foitzik T. Multiple organ failure in experimental pancr-eatitis[J]. Magy Seb， 2000， 53(6)：234-240.
18.	Frasquet JL， Sáez J， Trigo C， et al. Proteinuria and urinary beta 2-microglobulin as markers of tubular malfunction in the assessment of severity of acute pancreatitis[J]. Gastroenterol Hepatol， 2004， 27(5)：295-299.
19.	Nobiling R. The renin-angiotensin system：from the renal basis to an organ-specific subsystem in the pancreas[J]. JOP， 2001， 2(1)：9-12.
20.	He ZJ， Alho H， Harmoinen A， et al. Extrapancreatic multiorgan injury in a severe sublethal acute pancreatitis model[J]. Int J Surg Investig， 1999， 1(3)：177-184.
21.	Weber CK， Adler G. Acute pancreatitis[J]. Curr Opin Gastroenterol， 2003， 19(5)：447-450.
22.	Isenmann R， Rau B， Beger HG. Bacterial infection and extent of necrosis are determinants of organ failure in patients with acute necrotizing pancreatitis[J]. Br J Surg， 1999， 86(8)：1020-1024.
23.	Hoffmann TF， Leiderer R， Waldner H， et al. Bradykinin antag-onists HOE-140 and CP-0597 diminish microcirculatory injuryafter ischaemia-reperfusion of the pancreas in rats[J]. Br J Surg，.
24.	Raraty MG， Neoptolemos JP. Compartments that cause the real damage in severe acute pancreatitis[J]. Am J Respir Crit Care Med， 2003， 168(2)：141-142.
25.	Yücel K， Alhan E， Küçüktülü U， et al. The effects of prostagl-andin E1 on the microperfusion of the pancreas during acute necro-tizing pancreatitis in rats[J]. Hepatogastroenterology， 2002， 49(44)：544-548.
26.	， 83(2)：189-195.

1. Pezzilli R， Ceciliato R， Barakat B， et al. Immune-manipulation of the inflammatory response in acute pancreatitis. What can be expected?[J]. JOP， 2004， 5(3)：115-121.
2. Pezzilli R， Billi P， Morselli-Labate AM. Severity of acute pancr-eatitis：relationship with etiology， sex and age[J]. Hepatogastroenterology， 1998， 45(23)：1859-1864.
3. Mock BH， Wellman HN. Stoichiometric 99Tcm RBC labeling using stable kit solutions of stannous chloride and EDTA：concise communication[J]. J Nucl Med， 1984， 25(8)：881-886.
4. 王春友，赵玉沛. 重视重症急性胰腺炎多学科综合治疗[J]. 中国实用外科杂志， 2012， 32(7)：517-519.
5. Raraty MG， Connor S， Criddle DN， et al. Acute pancreatitis and organ failure：pathophysiology， natural history， and management strategies[J]. Curr Gastroenterol Rep， 2004， 6(2)：99-103.
6. Sha H， Ma Q， Jha RK. Trypsin is the culprit of multiple organ injury with severe acute pancreatitis[J]. Med Hypotheses， 2009， 72(2)：180-182.
7. 李文，郑芳，张集圣. 大承气汤对急性细菌性腹膜炎家兔重要脏器血流的影响[J]. 中国中西医结合外科杂志， 1999， 5(2)：114-116.
8. 雷文章，韦靖江，沈文律，等. 实验性坏死性胰腺炎多器官损害与内毒素血症的关系[J]. 中华实验外科杂志， 1995， 12(3)：131-132.
9. Uhlmann D. Microcirculatory disturbances in the pathogenesis ofacute pancreatitis. //Rodrigo L ed. Acute Pancreatitis[M]. Printedin Croatia， Pubiished by Intechweb. org. December 2011， 141-170.
10. Parmar MS. Pancreatic necrosis associated with preeclampsia-eclampsia[J]. JOP， 2004， 5(2)：101-104.
11. 崔培林，修瑞娟. 微循环障碍与急性胰腺炎[J]. 世界华人消化杂志， 2004， 12(12)：2853-2855.
12. Strate T， Mann O， Kleinhans H， et al. Systemic intravenous infusion of bovine hemoglobin significantly reduces microcirculatorydysfunction in experimentally induced pancreatitis in the rat[J]. Ann Surg， 2003， 238(5)：765-771.
13. Foitzik T， Eibl G， Hotz B， et al. Persistent multiple organ micro-circulatory disorders in severe acute pancreatitis：experimental findings and clinical implications[J]. Dig Dis Sci， 2002， 47(1)：130-138.
14. Menger MD， Bonkhoff H， Vollmar B， et al. Ischemia-reperfusion-induced pancreatic microvascular injury[J]. Dig Dis Sci， 1996， 41(5)：823-830.
15. Pelichovská M， Cvachovec K， Hoch J. Intensive care for patientswith severe acute pancreatitis with a significant multiorgan dysfu-nction[J]. Rozhl Chir， 2004， 83(9)：443-450.
16. Greenstein RJ， Krakoff LR， Felton K. Activation of the renin system in acute pancreatitis[J]. Am J Med， 1987， 82(3)：401-404.
17. Forgács B， Foitzik T. Multiple organ failure in experimental pancr-eatitis[J]. Magy Seb， 2000， 53(6)：234-240.
18. Frasquet JL， Sáez J， Trigo C， et al. Proteinuria and urinary beta 2-microglobulin as markers of tubular malfunction in the assessment of severity of acute pancreatitis[J]. Gastroenterol Hepatol， 2004， 27(5)：295-299.
19. Nobiling R. The renin-angiotensin system：from the renal basis to an organ-specific subsystem in the pancreas[J]. JOP， 2001， 2(1)：9-12.
20. He ZJ， Alho H， Harmoinen A， et al. Extrapancreatic multiorgan injury in a severe sublethal acute pancreatitis model[J]. Int J Surg Investig， 1999， 1(3)：177-184.
21. Weber CK， Adler G. Acute pancreatitis[J]. Curr Opin Gastroenterol， 2003， 19(5)：447-450.
22. Isenmann R， Rau B， Beger HG. Bacterial infection and extent of necrosis are determinants of organ failure in patients with acute necrotizing pancreatitis[J]. Br J Surg， 1999， 86(8)：1020-1024.
23. Hoffmann TF， Leiderer R， Waldner H， et al. Bradykinin antag-onists HOE-140 and CP-0597 diminish microcirculatory injuryafter ischaemia-reperfusion of the pancreas in rats[J]. Br J Surg，.
24. Raraty MG， Neoptolemos JP. Compartments that cause the real damage in severe acute pancreatitis[J]. Am J Respir Crit Care Med， 2003， 168(2)：141-142.
25. Yücel K， Alhan E， Küçüktülü U， et al. The effects of prostagl-andin E1 on the microperfusion of the pancreas during acute necro-tizing pancreatitis in rats[J]. Hepatogastroenterology， 2002， 49(44)：544-548.
26. ， 83(2)：189-195.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Urokinase on Severity Acute Pancreatitis with Renal Injury in Rat

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