Niederau C, Niederau M, Borchard F, Ude K, Lüthen R, Strohmeyer G, Ferrell L D, Grendell J H
Medizinische Klinik und Poliklinik, Abteilung für Gastroenterologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Pancreas. 1992;7(4):486-96. doi: 10.1097/00006676-199207000-00011.
The present studies were done to evaluate the therapeutic potential of several antioxidants and free radical scavengers in three different models of acute pancreatitis. (a) Edematous pancreatitis with acinar cells necrosis was induced by seven hourly intraperitoneal injections of 50 micrograms of caerulein per kg in mice. (b) Hemorrhagic pancreatitis was induced by feeding a choline-deficient, ethionine-supplemented (CDE) diet in mice. (c) Hemorrhagic pancreatitis was induced by retrograde infusion of 0.6 ml of 5% sodium taurocholate into the pancreatic duct in rats. The following antioxidants and free radical scavengers were given at various doses intravenously, subcutaneously, or intraperitoneally before the onset of pancreatitis: Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], superoxide dismutase, catalase, deferoxamine (Desferal), dimethyl sulfoxide, or allopurinol. The severity of pancreatitis was assessed at various times after its onset by determination of serum amylase and pancreatic weight (edema), by grading of histological alterations, and by determination of survival (survival determined in models of hemorrhagic pancreatitis). In general, free radical scavengers and antioxidants ameliorated edema and inflammation to a greater degree than necrosis and the increase in serum amylase. Superoxide dismutase (as did Ebselen in previous studies) exerted beneficial effects on survival in diet-induced pancreatitis in the absence of marked effects on pancreatic necrosis, suggesting that these beneficial effects are due to amelioration of extrapancreatic complications that often contribute to mortality in acute pancreatitis. None of the antioxidants had major beneficial effects in taurocholate-induced hemorrhagic pancreatitis. Thus, formation of free radicals may be important for progression and outcome in diet-induced and, to a lesser degree, in caerulein-induced pancreatitis but not at all in taurocholate-induced pancreatitis. Different models of pancreatitis may, therefore, involve different degrees and mechanisms of free radical formation. Despite the amelioration of edema and the beneficial effects on mortality seen for some antioxidants in some of the models, antioxidants and free radical scavengers appear to have only a limited potential for treatment of acute pancreatitis.
本研究旨在评估几种抗氧化剂和自由基清除剂在三种不同急性胰腺炎模型中的治疗潜力。(a) 通过每千克小鼠腹腔内每小时注射50微克蛙皮素，连续注射7次，诱导出伴有腺泡细胞坏死的水肿性胰腺炎。(b) 通过给小鼠喂食胆碱缺乏、添加乙硫氨酸（CDE）的饮食，诱导出出血性胰腺炎。(c) 通过向大鼠胰管逆行注入0.6毫升5%的牛磺胆酸钠，诱导出出血性胰腺炎。在胰腺炎发作前，以不同剂量静脉内、皮下或腹腔内给予以下抗氧化剂和自由基清除剂：依布硒啉[2-苯基-1,2-苯并异硒唑-3(2H)-酮]、超氧化物歧化酶、过氧化氢酶、去铁胺（得斯芬）、二甲亚砜或别嘌醇。在胰腺炎发作后的不同时间，通过测定血清淀粉酶和胰腺重量（水肿情况）、对组织学改变进行分级以及测定存活率（在出血性胰腺炎模型中测定存活率）来评估胰腺炎的严重程度。总体而言，自由基清除剂和抗氧化剂对水肿和炎症的改善程度大于对坏死和血清淀粉酶升高的改善程度。超氧化物歧化酶（如之前研究中的依布硒啉一样）对饮食诱导的胰腺炎的存活率产生有益影响，而对胰腺坏死无明显影响，这表明这些有益作用是由于改善了胰腺外并发症，而这些并发症往往是急性胰腺炎死亡的原因。在牛磺胆酸钠诱导的出血性胰腺炎中，没有一种抗氧化剂有显著的有益作用。因此，自由基的形成可能对饮食诱导的胰腺炎以及程度较轻的蛙皮素诱导的胰腺炎的进展和结局很重要，但对牛磺胆酸钠诱导的胰腺炎则完全不重要。因此，不同的胰腺炎模型可能涉及不同程度和机制的自由基形成。尽管在某些模型中一些抗氧化剂改善了水肿并对死亡率产生了有益影响，但抗氧化剂和自由基清除剂在治疗急性胰腺炎方面的潜力似乎有限。
