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褪黑素治疗糖尿病中肾缺血再灌注损伤诱导的远隔器官损伤。

Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus.

作者信息

Fadillioglu Ersin, Kurcer Zehra, Parlakpinar Hakan, Iraz Mustafa, Gursul Cebrail

机构信息

Faculty of Medicine, Department of Physiology, Hacettepe University, Ankara, 06100, Turkey.

出版信息

Arch Pharm Res. 2008 Jun;31(6):705-12. doi: 10.1007/s12272-001-1216-3. Epub 2008 Jun 19.

Abstract

Oxidative stress may have a role in liver damage after acute renal injury due to various reasons such as ischemia reperfusion (IR). Diabetes mellitus (DM) is an important disease for kidneys and may cause nephropathy as a long term complication. The aim of this study was to investigate protective effect of melatonin, a potent antioxidant, against distant organ injury on liver induced by renal IR in rats with or without DM. The rats were divided into six groups: control (n=7), DM (n=5), IR (n=7), DM+IR (n=7), melatonin+IR (Mel+IR) (melatonin, 4 mg/ kg during 15 days) (n=7), and Mel+DM+IR groups (n=7). Diabetes developed 3 days after single i.p. dose of 45 mg/kg streptozotocin. After 15 day, the left renal artery was occluded for 30 min followed 24 h of reperfusion in IR performed groups. DM did not alter oxidative parameters alone in liver tissue. The levels of malondialdehyde, protein carbonyl and nitric oxide with activities of xanthine oxidase and myeloperoxidase were increased in liver tissues of diabetic and non-diabetic IR groups. Nitric oxide level in DM was higher than control. The activities of catalase and superoxide dismutase were increased in IR groups in comparison with control and DM. ALT and AST levels were higher in IR and DM+IR groups than control and DM. Melatonin treatment reversed all these oxidant and antioxidant parameters to control values as well as serum liver enzymes. We concluded that renal IR may affect distant organs such as liver and oxidative stress may play role on this injury, but DM has not an effect on kidney induced distant organ injury via oxidant stress. Also, it was concluded that melatonin treatment may prevent liver oxidant stress induced by distant injury of kidney IR.

摘要

氧化应激可能在因各种原因(如缺血再灌注(IR))导致的急性肾损伤后的肝损伤中起作用。糖尿病(DM)是一种重要的肾脏疾病,可能作为长期并发症导致肾病。本研究的目的是探讨褪黑素(一种有效的抗氧化剂)对有或无糖尿病的大鼠肾IR诱导的肝脏远处器官损伤的保护作用。大鼠被分为六组:对照组(n = 7)、糖尿病组(n = 5)、IR组(n = 7)、糖尿病 + IR组(n = 7)、褪黑素 + IR组(Mel + IR)(褪黑素,4 mg/kg,持续15天)(n = 7)和Mel + 糖尿病 + IR组(n = 7)。单次腹腔注射45 mg/kg链脲佐菌素3天后诱导糖尿病。15天后,IR组将左肾动脉阻断30分钟,随后再灌注24小时。糖尿病单独不会改变肝脏组织中的氧化参数。糖尿病和非糖尿病IR组肝脏组织中的丙二醛、蛋白质羰基和一氧化氮水平以及黄嘌呤氧化酶和髓过氧化物酶的活性增加。糖尿病组中的一氧化氮水平高于对照组。与对照组和糖尿病组相比,IR组中的过氧化氢酶和超氧化物歧化酶活性增加。IR组和糖尿病 + IR组中的谷丙转氨酶和谷草转氨酶水平高于对照组和糖尿病组。褪黑素治疗将所有这些氧化和抗氧化参数以及血清肝酶恢复到对照值。我们得出结论,肾IR可能影响远处器官如肝脏,氧化应激可能在这种损伤中起作用,但糖尿病不会通过氧化应激对肾脏诱导的远处器官损伤产生影响。此外,得出结论,褪黑素治疗可能预防肾IR远处损伤诱导的肝脏氧化应激。

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