吡咯列酮对雨蛙肽诱导急性胰腺炎氧化应激过程的作用

The effects of pioglitazone on the process of oxidative stress in acute pancreatitis induced by cerulein

目的 探讨过氧化物酶体增殖物激活受体（PPAR）7激动剂吡咯列酮在雨蛙肽诱导大鼠急性胰腺炎中对氧化应激产物的影响及保护作用。方法30只雄性SD大鼠随机分为对照组、雨蛙肽＋不同剂量吡咯列酮组、雨蛙肽组、雨蛙肽＋吡咯列酮＋GW9662组，每组6只。急性胰腺炎造模30min后处死大鼠，光镜下观察胰腺组织病理学变化，测定各组大鼠胰腺组织质量与体重比，比色法检测胰腺组织髓过氧化物酶（MPO）活性、丙二醛（MDA）和一氧化氮合酶（NOS）及组织诱导型一氧化氮合酶（iNOS）含量。结果与对照组比较，雨蛙肽组胰腺组织水肿严重[胰腺净重／体重（0．0072比0．0042）]，MPO活性、MDA、NOS及iNOS含量升高（P〈0．01）。与雨蛙肽组比较，吡咯列酮20mg／kg及40mg／kg组胰腺损伤减轻，胰腺净重／体重、MPO活性、MDA和NOS及iNOS含量降低（P〈0．05）；与吡咯列酮40mg／kg组比较，PPAR7拮抗剂GW9662逆转了吡咯列酮的保护作用（P＜0．05）。结论在雨蛙肽诱导的大鼠急性胰腺炎发病中，胰腺腺泡细胞的氧化应激损伤起了重要的作用，PPAR7激动剂吡咯列酮预先干预，通过降低氧化应激过程，对雨蛙肽诱导的大鼠急性胰腺炎有一定的保护作用。

Objective To investigate the effects of pioglitazone, a peroxisome proliferation activated receptor （PPAR）γ agonist on oxidative stress process and the therapeutic effects on severity of acute pancreatitis （AP）. Methods Thirty male Sprague-Dawley rats were randomly divided into five groups with 6 in each： control group, cerulein plus pioglitazone group, cerulein group, cerulein plus vehicle group, cerulein plus pioglitazone and GW9662 group. Rats were sacrificed at 30 min after the induction of pancreatitis. Pathologic changes of the pancreas were observed under light microscope. The ratios of pancreatic wet/body weight of rat were determined in each group. Serum amylase, pancreatic nitric oxide synthase （NOS）, inducible nitric oxide synthase （iNOS）, malondialdehyde （MDA）, and myeloperoxidase （MPO） were determined by chromometry. Results The serum amylase, pancreatic wet/body weight and the score of pathologic damage increased after the induction of pancreatitis, AP samples were characterized by increased pancreatic MDA, MPO, NOS and iNOS（P〈0. 01）. Pioglitazone （20 mg/kg and 40 mg/kg） exhibited a protective effect against oxygen free radicals reflected by lower serum amylase, less severe pancreatic lesions, normal pancreatic MDA, MPO and NOS levels （P〈0. 05）. GW9662 reversed the effects against oxidative stress of pioglitazone （40 mg/kg）（P〈0.05）. Conclusions Pretreatment with pioglitazone may exert its therapeutic effect on AP by lowering pancreatic oxidative free radicals and reducing pancreatic tissue infiltration of neutrophils.