Pieper G M, Jordan M, Dondlinger L A, Adams M B, Roza A M
Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee 53226, USA.
Diabetes. 1995 Aug;44(8):884-9. doi: 10.2337/diab.44.8.884.
Diabetic complications are believed to arise, in part, through an increase in oxidative stress. We characterized antioxidant status in vascular tissue in untreated diabetic rats and in diabetic rats rendered euglycemic by pancreatic islet transplantation. Three key endogenous antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) were measured. Sprague-Dawley rats with streptozotocin-induced diabetes were killed after 8 weeks of untreated hyperglycemia and compared with age-matched controls. Eight weeks of untreated diabetes resulted in a significant increase of tissue catalase in aorta, iliac artery, and femoral artery as compared with controls. No significant changes in either superoxide dismutase or glutathione peroxidase were observed in aorta, iliac artery, or femoral artery of diabetic animals. This increase in catalase in diabetic vascular tissue suggests increased oxidative stress due to chronic exposure to H2O2 in vivo. To assess the impact of islet transplantation on oxidative stress in vascular tissue, inbred Lewis strain rats were rendered diabetic with streptozotocin. After 8 weeks of untreated diabetes, rats received an intraportal islet isograft and were monitored for 4 subsequent weeks of euglycemia. Islet transplantation improved weight gain and normalized blood glucose and total glycosylated hemoglobin. While catalase was significantly increased in aorta and iliac artery at 8 and 12 weeks of diabetes, vascular catalase was restored to normal by islet transplantation. These data suggest that islet transplantation is an effective treatment strategy to minimize increased oxidative stress in diabetic vasculature.
糖尿病并发症被认为部分是由氧化应激增加引起的。我们对未经治疗的糖尿病大鼠以及通过胰岛移植实现血糖正常的糖尿病大鼠的血管组织抗氧化状态进行了表征。测量了三种关键的内源性抗氧化酶（如超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶）。将链脲佐菌素诱导糖尿病的斯普拉格-道利大鼠在未经治疗的高血糖8周后处死，并与年龄匹配的对照组进行比较。与对照组相比，未经治疗的糖尿病8周导致主动脉、髂动脉和股动脉中的组织过氧化氢酶显著增加。在糖尿病动物的主动脉、髂动脉或股动脉中未观察到超氧化物歧化酶或谷胱甘肽过氧化物酶有显著变化。糖尿病血管组织中过氧化氢酶的这种增加表明由于体内长期暴露于过氧化氢导致氧化应激增加。为了评估胰岛移植对血管组织氧化应激的影响，用链脲佐菌素使近交系刘易斯大鼠患糖尿病。未经治疗的糖尿病8周后，大鼠接受门静脉内胰岛同种异体移植，并在随后的4周血糖正常期间进行监测。胰岛移植改善了体重增加，并使血糖和总糖化血红蛋白恢复正常。虽然糖尿病8周和12周时主动脉和髂动脉中的过氧化氢酶显著增加，但胰岛移植使血管过氧化氢酶恢复正常。这些数据表明，胰岛移植是一种有效的治疗策略，可将糖尿病血管中增加的氧化应激降至最低。
