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Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

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World Journal of Gastroenterology 2005年第40期11卷 6322-6329页

作者： Peter C Konturek Artur dembinski Zygmunt Warzecha Grzegorz Burnat Piotr Ceranowicz Eckhart G Hahn marcin dembinski Romana Tomaszewska Stanislaw J Konturek Department of Physiology

AIM： To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-y （PPART） ligand, on the development of acute pancreatitis （AP） and on the expression of heat shock protein 70 （HSP70） in the pancreas. METHODS： AP was induced in rats by subcutaneous infusion of ceruw was measured by laser Dopplein for 5 h. Pancreatic blood floler flowmetry. Plasma lipase activity, intedeukin-1β （IL-1β） and IL-10 were determined. Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein. RESULTS： Pioglitazone administered （10-100 mg/kg i.g.） 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis （tiP） as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment. CONCLUSION： Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-infiammatory activities, to the suppression of IL-1β and to the overexpression of HSP70. PPART ligands could represent a new therapeutic optionin the treatment of AP.

关键词： Cerulein-induced pancreatitis PPARy, ligand Heat shock protein 70

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Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: Involvement of cyclooxygenases and heat shock protein 70

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World Journal of Gastroenterology 2005年第38期11卷 5958-5965页

作者： Zygmunt Warzecha Artur dembinski Piotr Ceranowicz Stanislaw J Konturek marcin dembinski Wieslaw W Pawlik Romana Tomaszewska Jerzy Stachura Beata Kusnierz-Cabala Jerzy W Naskalski Peter C Konturek Department of Physiology Department of Pathology Department of Clinical Biochemistry Department of Internal Medicine Ⅰ

AIM： To determine whether ischemic preconditioning （IP） affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 （COX-l）, COX-2, and heat shock protein 70 （HSP 70） in this process. METHODS： In male Wistar rats, IP was performed by damping 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 resverabol or rofecoxib, respectively （10 rng/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）-1β. 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 reducespancreatic 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

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