Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis
Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis
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DOI：
10.3748/wjg.v11.i40.6322
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发表时间：
2005-10-28
影响因子：
4.3
通讯作者：
Konturek, Stanislaw J.
中科院分区：
文献类型：
--
作者：
Konturek, Peter C.;Dembinski, Artur;Konturek, Stanislaw J.
目的：目的：探讨过氧化物酶体增殖物激活受体-γ（peroxisomeproliferator-activatedreceptor-gamma，PPAR-gamma）特异性配体吡格列酮对急性胰腺炎（acutepancreatitis，AP）发生、发展及胰腺热休克蛋白70（heatshockprotein 70，HSP 70）表达的影响。用激光多普勒血流仪测量胰腺血流量。测定血浆脂肪酶活性、白细胞介素-1 β（IL-1 β）和IL-10。在用吡格列酮单独或与雨蛙肽组合处理的大鼠中评估胰腺重量和组织学，并评估胰腺DNA合成和血流量以及胰腺IL-1 β和HSP 70的mRNA。在蛙皮素诱导胰腺炎（CIP）前30分钟，剂量依赖性地减轻胰腺组织损伤，如胰腺组织学的改善、血浆脂肪酶活性的降低、促炎性IL-1 β的血浆浓度及其在胰腺中的基因表达以及胰腺炎诱发的胰腺血流量下降的减弱所证明的。CIP增加胰腺HSP 70的mRNA和蛋白表达在胰腺和这种效果是由吡格列酮增强treatment.CONCLUSION：吡格列酮衰减CIP和这种吡格列酮的有益效果可能是多因素的，由于其抗炎活性，抑制IL-1 β和HSP 70的过度表达。PPARgamma配体可能代表AP治疗的一种新的治疗选择。(C)2005年WJG出版社和Elsevier Inc. All rights reserved.
AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-gamma (PPAR gamma) 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 cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1 beta (IL-1 beta) 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-1 beta 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 (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1 beta 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-inflammatory activities, to the suppression of IL-1 beta and to the overexpression of HSP70. PPAR gamma ligands could represent a new therapeutic option in the treatment of AP. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.