Chen Chen, Xu Sheng, Wang Wei-Xing, Ding You-Ming, Yu Kai-Huan, Wang Bin, Chen Xiao-Yan
Department of General Surgery, Renmin Hospital of Wuhan University, PR China.
Arch Med Res. 2009 Feb;40(2):79-88. doi: 10.1016/j.arcmed.2008.11.004. Epub 2009 Jan 21.
In addition to the effect of regulating adipocyte differentiation and insulin sensitivity, peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligands also exhibit anti-inflammatory effect. However, the mechanisms concerning how PPAR-gamma ligands affect acute pancreatitis and pancreatitis-associated lung injury have not been fully elucidated. This study investigated the effect of rosiglitazone, a PPAR-gamma ligand, on acute pancreatitis and pancreatitis-associated lung injury in the rat pancreatitis model induced by sodium taurocholate.
Acute pancreatitis was induced by retrograde infusion of 5% sodium taurocholate (1 mL/kg) into the bile-pancreatic duct. Rosiglitazone (6 mg/kg) was administered via the femoral vein 30 min prior to the infusion of sodium taurocholate. The severity of pancreatitis was evaluated by serum amylase level, myeloperoxidase activity, and pathology. Pancreatitis-associated lung injury was evaluated by myeloperoxidase activity, the magnitude of pulmonary edema and pathology. Intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha mRNA expression were studied using reverse transcriptase polymerase chain reaction. ICAM-1 protein expression was studied using Western blot analysis.
Prophylactic administration of rosiglitazone attenuated (1) serum amylase level; (2) myeloperoxidase activity of pancreatic and pulmonary tissue; (3) expression of tumor necrosis factor-alpha and ICAM-1 in pancreas and lung; (4) pancreas and lung pathological damage.
Our study demonstrated that rosiglitazone exerts a protective effect against sodium taurocholate-induced pancreatic and pulmonary injury.
过氧化物酶体增殖物激活受体γ（PPAR-γ）配体除了具有调节脂肪细胞分化和胰岛素敏感性的作用外，还具有抗炎作用。然而，PPAR-γ配体影响急性胰腺炎及胰腺炎相关性肺损伤的机制尚未完全阐明。本研究在牛磺胆酸钠诱导的大鼠胰腺炎模型中，探讨PPAR-γ配体罗格列酮对急性胰腺炎及胰腺炎相关性肺损伤的影响。
通过逆行向胆胰管内注入5%牛磺胆酸钠（1 mL/kg）诱导急性胰腺炎。在注入牛磺胆酸钠前30分钟经股静脉给予罗格列酮（6 mg/kg）。通过血清淀粉酶水平、髓过氧化物酶活性及病理学评估胰腺炎的严重程度。通过髓过氧化物酶活性、肺水肿程度及病理学评估胰腺炎相关性肺损伤。采用逆转录聚合酶链反应研究细胞间黏附分子-1（ICAM-1）和肿瘤坏死因子-α mRNA表达。采用蛋白质印迹分析研究ICAM-1蛋白表达。
预防性给予罗格列酮可减轻：（1）血清淀粉酶水平；（2）胰腺和肺组织的髓过氧化物酶活性；（3）胰腺和肺中肿瘤坏死因子-α和ICAM-1的表达；（4）胰腺和肺的病理损伤。
我们的研究表明，罗格列酮对牛磺胆酸钠诱导的胰腺和肺损伤具有保护作用。
