Furukawa F, Nishikawa A, Kasahara K, Miyauchi M, Nakamura H, Son H Y, Uchida K, Hirose M
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
Pancreas. 2001 May;22(4):427-30. doi: 10.1097/00006676-200105000-00014.
To cast light on the mechanisms underlying development of spontaneous pancreatitis lesions, tissues from WBN/Kob rats at various ages were histopathologically and immunohistochemically investigated with special reference to the existence of the lipid peroxidation products 4-hydroxy-2-nonenal (HNE), 4-hydroxy-2-hexenal (HHE), and malondialdehyde (MDA). Male 4-20-week-old WBN/Kob rats were killed to allow sampling of pancreatic tissues, which were fixed in cold acetone and 10% neutral-buffered formalin. and then processed for routine histopathology as well as immunohistochemistry for proteins modified by HNE, HHE, and MDA. Although no remarkable histologic changes were noted in younger animals, edema, hemorrhage, inflammatory cell infiltration, fibrosis, vacuolation of acinar cells, and ductular proliferation were observed in exocrine pancreatic tissue from animals at 10-15 weeks of age. In animals aged 20 weeks, the lesions had progressed remarkably and deposits of hemosiderin were apparent with fibrosis. Immunohistochemical examination for lipid peroxidation product-modified proteins showed HNE and MDA to be negative in all pancreatic tissues, but HHE was positive in the areas involving atrophy of acinar cells and fibrosis in the islets. The results of the present study thus provide support for the conclusion that lipid peroxidation during spontaneous pancreatitis in WBN/Kob rats may possibly be involved in the development of diabetes in this model.
为了阐明自发性胰腺炎病变发展的潜在机制，对不同年龄段的WBN/Kob大鼠组织进行了组织病理学和免疫组织化学研究，特别关注脂质过氧化产物4-羟基-2-壬烯醛（HNE）、4-羟基-2-己烯醛（HHE）和丙二醛（MDA）的存在情况。处死4至20周龄的雄性WBN/Kob大鼠以获取胰腺组织样本，将其固定在冷丙酮和10%中性缓冲福尔马林中，然后进行常规组织病理学检查以及针对经HNE、HHE和MDA修饰的蛋白质的免疫组织化学检查。虽然在较年轻的动物中未观察到明显的组织学变化，但在10至15周龄动物的胰腺外分泌组织中观察到水肿、出血、炎性细胞浸润、纤维化、腺泡细胞空泡化和导管增生。在20周龄的动物中，病变进展显著，出现含铁血黄素沉积并伴有纤维化。脂质过氧化产物修饰蛋白的免疫组织化学检查显示，所有胰腺组织中的HNE和MDA均为阴性，但HHE在涉及腺泡细胞萎缩和胰岛纤维化的区域呈阳性。因此，本研究结果支持以下结论：WBN/Kob大鼠自发性胰腺炎期间的脂质过氧化可能参与了该模型中糖尿病的发生发展。
