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糖尿病肾病中的抗氧化防御系统:一项时间进程研究。

Antioxidant defense system in diabetic kidney: a time course study.

作者信息

Kakkar R, Mantha S V, Radhi J, Prasad K, Kalra J

机构信息

Department of Pathology and Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.

出版信息

Life Sci. 1997;60(9):667-79. doi: 10.1016/s0024-3205(96)00702-3.

Abstract

Oxygen free radicals (OFRs) have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level measured as thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes viz., [superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px)] in the kidney of streptozotocin induced diabetic rats at various stages of development of diabetes. Sprague Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups each consisting of six rats. Rats in subgroups were studied at weekly intervals (0 to 6 weeks). Blood glucose levels were estimated at the time of sacrifice. TBARS levels and activity of antioxidant enzymes were measured in kidney. The levels of TBARS in the diabetic group increased initially, dropped to baseline level after 2 weeks and then progressively increased at 5th and 6th week (p < 0.05). There was an increase in catalase activity at first week after that it decreased as compared to control group. However, GSH-Px activity in the diabetic group increased after 1 week and then remained at the same level except a small drop in the 2nd week. Total SOD and CuZn-SOD activity increased significantly in diabetic kidney as compared to controls at all time intervals, while Mn-SOD activity showed no change. The present findings suggest that oxidative stress accompanies at early onset of diabetes mellitus and the susceptibility of the kidney to oxidative stress during the early stages may be an important factor in the development of diabetic nephropathy.

摘要

氧自由基(OFRs)被认为是糖尿病并发症的一个促成因素。在本研究中,我们调查了链脲佐菌素诱导的糖尿病大鼠在糖尿病发展的各个阶段肾脏中以硫代巴比妥酸反应性物质(TBARS)衡量的脂质过氧化物水平以及抗氧化酶[超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)]的活性。将斯普拉格-道利大鼠分为两组:第一组为对照组(n = 42),第二组为糖尿病组(n = 42)。每组再进一步细分为七组,每组六只大鼠。对亚组大鼠每隔一周(0至6周)进行研究。在处死时估计血糖水平。测量肾脏中TBARS水平和抗氧化酶活性。糖尿病组的TBARS水平最初升高,2周后降至基线水平,然后在第5周和第6周逐渐升高(p < 0.05)。过氧化氢酶活性在第一周增加,之后与对照组相比下降。然而,糖尿病组的GSH-Px活性在1周后增加,然后保持在同一水平,除了在第2周有小幅下降。与对照组相比,糖尿病肾脏中的总SOD和CuZn-SOD活性在所有时间间隔均显著增加,而Mn-SOD活性无变化。目前的研究结果表明,氧化应激在糖尿病发病早期就存在,并且在早期阶段肾脏对氧化应激的易感性可能是糖尿病肾病发展的一个重要因素。

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