Nonaka A, Manabe T, Kyogoku T, Tamura K, Tobe T
First Department of Surgery, Faculty of Medicine, Kyoto University.
Nihon Shokakibyo Gakkai Zasshi. 1990 May;87(5):1212-6.
In order to clarify the role of free radicals in the pathogenesis of acute pancreatitis, we observed the effect of a new synthetic free radical scavenger (CV-3611) on the pathological state in the models of both caerulein and CDE-diet induced acute pancreatitis in mice. In both models of acute pancreatitis, the levels of serum amylase activity were reduced significantly by the treatment of CV-3611. Pancreatic edema formation was also reduced significantly at 3.5 and 9 h after the first caerulein i.p. injection. The 4 days survival rate in CDE-diet induced pancreatitis was significantly elevated from 41.2% to 81.3% by the treatment of CV-3611. These results indicate that this synthetic scavenger, which has a long circulation half life, high affinity to biomembrane and good cell penetration ability, is effective on the development of both severe and mild pancreatitis. The main pathogenesis of both models is suggested to be radical reactions on the biomembrane which is caused by the interreaction between endothelium and neurophile in caerulein induced pancreatitis, and by the lipid peroxidation on the biomembrane of the organella in the cell in CDE-diet induced pancreatitis.
为了阐明自由基在急性胰腺炎发病机制中的作用，我们观察了一种新型合成自由基清除剂（CV - 3611）对小鼠蛙皮素和CDE饮食诱导的急性胰腺炎模型病理状态的影响。在两种急性胰腺炎模型中，CV - 3611治疗均显著降低了血清淀粉酶活性水平。在首次腹腔注射蛙皮素后3.5小时和9小时，胰腺水肿形成也显著减轻。CV - 3611治疗使CDE饮食诱导的胰腺炎4天生存率从41.2%显著提高到81.3%。这些结果表明，这种具有长循环半衰期、对生物膜具有高亲和力和良好细胞穿透能力的合成清除剂，对重症和轻症胰腺炎的发展均有效。两种模型的主要发病机制被认为是：在蛙皮素诱导的胰腺炎中，由内皮细胞与嗜神经细胞之间的相互作用引起生物膜上的自由基反应；在CDE饮食诱导的胰腺炎中，由细胞内细胞器生物膜上的脂质过氧化引起。
