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Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: Involvement of cyclooxygenases and heat shock protein 70
作者姓名:Warzecha Z  Dembinski A  Ceranowicz P  Konturek SJ  Dembinski M  Pawlik WW  Tomaszewska R  Stachura J  Kusnierz-Cabala B  Naskalski JW  Konturek PC
作者单位:Department of Physiology,Department of Physiology,Department of Physiology,Department of Physiology,Department of Physiology,Department of Physiology,Department of Pathology,Department of Pathology,Department of Clinical Biochemistry,Department of Clinical Biochemistry,Department of Internal Medicine Ⅰ Jagiellonian University Medical College,Kraków,Poland Jagiellonian University Medical College,Kraków,Poland Jagiellonian University Medical College,Kraków,Poland Jagiellonian University Medical College,Kraków,Poland Jagiellonian University Medical College,Kraków,Poland Jagiellonian University Medical College,Kraków,Poland,Jagiellonian University Medical College,Kraków,Poland,Jagiellonian University Medical College,Kraków,Poland,Jagiellonian University Medical College,Kraków,Poland,Jagiellonian University Medical College,Kraków,Poland,University of Erlangen-Nuremberg,Erlangen,Germany
摘    要:AIM: To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process, METHODS: In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg). RESULTS: IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-lp. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis. CONCLUSION: Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.

关 键 词:Acute  pancreatitis  Ischemic  preconditioning  Cyclooxygenase-2  Interleukin-1β  Heat  shock  protein-70
收稿时间:2004 Dec 17

Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: involvement of cyclooxygenases and heat shock protein 70
Warzecha Z,Dembinski A,Ceranowicz P,Konturek SJ,Dembinski M,Pawlik WW,Tomaszewska R,Stachura J,Kusnierz-Cabala B,Naskalski JW,Konturek PC.Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: involvement of cyclooxygenases and heat shock protein 70[J].World Journal of Gastroenterology,2005,11(38):5958-5965.
Authors:Warzecha Zygmunt  Dembinski Artur  Ceranowicz Piotr  Konturek Stanislaw-J  Dembinski Marcin  Pawlik Wieslaw-W  Tomaszewska Romana  Stachura Jerzy  Kusnierz-Cabala Beata  Naskalski Jerzy-W  Konturek Peter-C
Institution:1. Department of Physiology, Jagiellonian University Medical College,Kraków, Poland
2. Department of Pathology,Jagiellonian University Medical College, Kraków, Poland
3. Department of Clinical Biochemistry, Jagiellonian University Medical College,Kraków, Poland
4. Department of Internal Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany
Abstract:AIM: To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process, METHODS: In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg). RESULTS: IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-lp. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis. CONCLUSION: Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.
Keywords:Acute pancreatitis  Ischemic preconditioning  Cyclooxygenase-2  Interleukin-1β  Heat shock protein-70
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