Nonaka A, Manabe T, Kyogoku T, Tamura K, Tobe T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Dig Dis Sci. 1992 Feb;37(2):274-9. doi: 10.1007/BF01308183.
To define the role of free radicals and of lipid peroxide involvement during the progress of cerulein-induced acute pancreatitis in mice, we evaluated the effect of a novel free radical scavenger, 2-octadecylascorbic acid (CV-3611), on pancreatic edema formation, and the levels of serum enzymes (amylase, lipase) and of lipid peroxide in pancreatic tissue. Mice were divided into three groups: control group, intraperitoneal injection of saline only; pancreatitis group, cerulein 50 micrograms/kg injected intraperitoneally six times at 1-hr intervals; treatment groups, CV-3611 10 mg/kg subcutaneously just after intraperitoneal cerulein injection. After the cerulein injection, the degree of pancreatic edema formation, serum amylase and lipase levels, and the amount of lipid peroxide in pancreatic tissue increased significantly during the observation period of 12 hr. Treatment with CV-3611 resulted in significant reduction in pancreatic edema formation at 3.5 hr (P less than 0.05) and 9 hr (P less than 0.05), serum amylase and lipase levels at 3.5 hr (P less than 0.05) and 12 hr (P less than 0.05), and lipid peroxide levels at 3.5 hr (P less than 0.05), 6 hr (P less than 0.05) and 12 hr (P less than 0.05). These results indicate that a novel free radical scavenger, CV-3611, has a strong therapeutic effect during the development of acute pancreatitis and suggest that oxygen-derived free radicals play an important role in the pathogenesis of acute pancreatitis.
为明确自由基及脂质过氧化物在小鼠雨蛙肽诱导的急性胰腺炎进展过程中的作用，我们评估了一种新型自由基清除剂2-十八烷基抗坏血酸（CV-3611）对胰腺水肿形成、血清酶（淀粉酶、脂肪酶）水平及胰腺组织中脂质过氧化物水平的影响。将小鼠分为三组：对照组，仅腹腔注射生理盐水；胰腺炎组，以50微克/千克的雨蛙肽腹腔注射，每隔1小时注射1次，共注射6次；治疗组，在腹腔注射雨蛙肽后立即皮下注射10毫克/千克的CV-3611。注射雨蛙肽后，在12小时的观察期内，胰腺水肿形成程度、血清淀粉酶和脂肪酶水平以及胰腺组织中脂质过氧化物的量均显著增加。CV-3611治疗导致在3.5小时（P<0.05）和9小时（P<0.05）时胰腺水肿形成显著减轻，在3.5小时（P<0.05）和12小时（P<0.05）时血清淀粉酶和脂肪酶水平显著降低，在3.5小时（P<0.05）、6小时（P<0.05）和12小时（P<0.05）时脂质过氧化物水平显著降低。这些结果表明，新型自由基清除剂CV-3611在急性胰腺炎发展过程中具有强大的治疗作用，并提示氧衍生自由基在急性胰腺炎发病机制中起重要作用。
