还原型谷胱甘肽对实验性急性坏死性胰腺炎的治疗效果及机制

Effect and mechanism of reduced glutathione treatment in experimental acute necrotizing pancreatitis.

目的探讨还原型谷胱甘肽（GSH）对实验性ANP的疗效及其机制。方法54只雄性Sprague-Dawley大鼠随机分为对照组（NS）、ANP组、GSH干预组（GSH组）3组,每组再分成3h、6h和12h3组。经胆胰管内注射3.5%牛磺胆酸钠0.1ml/100g体重制备ANP模型。GSH组在制模后即刻腹腔注射GSH12.5mg/100g体重。检测各组不同时间点血淀粉酶、超氧化物歧化酶（SOD）及丙二醛（MDA）含量,并取胰腺组织常规病理检查,RT-PCR法和免疫组织化学法检测胰腺组织中NF-κBp65 mRNA及蛋白表达。结果GSH 3h、6h组胰腺组织病理分值、血清淀粉酶、MDA含量、NF-κBp65 mRNA及蛋白表达较同时点ANP组明显减弱（P〈0.05）;血清SOD明显增加（P〈0.05）。结论GSH腹腔注射后短期内能够改善ANP大鼠的胰腺组织损害,其机制可能通过抗氧自由基及抑制胰腺组织NF-κB的表达而发挥作用。

Objective To investigate the therapeutic effects and possible mechanism of reduced glutathione in experimental severe acute pancreatitis. Methods Fifty four male Sprague-Dawley rats were randomly divided into three groups., saline control group, acute necrotizing pancreatitis （ANP） group and reduced glutathione treated group （GSH）. ANP was reproduced by retrograde injection of 3.5% Sodium taurocholate. Animals in each group were sacrificed at 3, 6 and 12 hours after induction of ANP. GSH treated groups were given GSH at a dosage of 12.5 mg/100 g body weight. Intrapancreatic NF-κB, p65 and mRNA expression were assayed by immunohistochemistry and RT-PCR. The following parameters were also measured： serum amylase, superoxide dismutase （SOD）, Maleic Dialdehyde （MDA） and histological grading of pancreas injury. Results The histological grading of pancreas injury, serum level of serum amylase, MDA, NF-KB, p65 and mRNA in GSH-treated group were significantly lower than those in ANP group at respective time-points （P 〈 0.05 ）, however, the level of serum SOD in GSH-treated group significantly increased compared to that in ANP group （P 〈 0.05）. Conclusions Intraperitoneally administrated GSH reduced pancreatic tissue damage in ANP rats in short term, and the possible mechanism may be inhibiting pancreatic expression of NF-KB and oxygen free radicals.