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α-生育酚可改善脊髓再灌注损伤相关的氧化肾损伤。

Alpha-tocopherol ameliorates oxidative renal insult associated with spinal cord reperfusion injury.

机构信息

Physiology Department, Faculty of Medicine, King Khalid University, Abha, Saudi Arabia.

出版信息

J Physiol Biochem. 2013 Sep;69(3):487-96. doi: 10.1007/s13105-013-0236-9. Epub 2013 Jan 24.

Abstract

Ischemic-reperfusion procedures targeting a specific organ often results in remote multiple organ injuries mediated possibly by heightened oxidative stress levels. As the kidney is one of the most vulnerable organs for ischemic oxidative stress, the aim of the present study was to confirm the occurrence of renal complication secondary to spinal cord ischemic-reperfusion injury (SC-IRI) induced by aortic clamping. The study also investigated the possible prophylactic effect of long-term administration of α-tocopherol (α-TOL) against high level of renal oxidative stress and inflammatory processes induced by SC-IRI. In this study, a total of 60 male Sprague-Dawley rats were randomly divided into five equal groups: C group underwent no surgery; CE group received α-TOL 600 mg/kg intramuscular twice weekly for 6 weeks; S group were subjected to laparotomy without clamping of the aorta; SE group were handled as S group and treated with α-TOL as group CE; SC-IRI group were subjected to laparotomy with clamping of the aorta just above the bifurcation of the aorta for 45 min, then the clamp was released for 48 h for reperfusion. SC-IRIE group was subjected to IRI as in group SC-IRI and was injected with α-TOL in the same dose and route as α-TOL-treated control group. SC-IRI resulted in increases in serum creatinine, blood urea nitrogen, plasma nitrite/nitrate level, serum tumor necrosis factor alpha, renal tissue homogenate level for malondialdehyde, superoxide dismutase and prostaglandin E2. Long-term prophylactic treatment with α-TOL resulted in amelioration of the renal functional disturbances and all measured parameters of oxidative stress and inflammation. Ischemic reperfusion injury of the spinal cord induced some remote renal functional disturbances although some of the observed changes may have resulted from decreased renal blood flow due to the hypotension induced during the procedure. Prophylactic long-term α-TOL administration guards against the renal function disturbances an effect that can be attributed, at least partially, to improvement of the renal pro-oxidant/antioxidant balance and inhibition of the inflammatory processes.

摘要

针对特定器官的缺血再灌注程序通常会导致远程多器官损伤,这可能是由氧化应激水平升高介导的。由于肾脏是对缺血性氧化应激最敏感的器官之一,因此本研究的目的是确认由主动脉夹闭引起的脊髓缺血再灌注损伤(SC-IRI)继发的肾并发症的发生。该研究还调查了长期给予α-生育酚(α-TOL)对 SC-IRI 引起的高水平肾氧化应激和炎症过程的可能预防作用。在这项研究中,总共 60 只雄性 Sprague-Dawley 大鼠被随机分为五组:C 组不进行手术;CE 组每周肌肉注射α-TOL 600mg/kg 两次,共 6 周;S 组进行剖腹手术,但不夹闭主动脉;SE 组作为 S 组处理,同时给予 α-TOL 作为 CE 组;SC-IRI 组进行剖腹手术,在主动脉分叉上方夹闭主动脉 45 分钟,然后释放夹闭 48 小时再灌注。SC-IRIE 组接受与 SC-IRI 组相同的 IRI,并以与α-TOL 治疗对照组相同的剂量和途径注射α-TOL。SC-IRI 导致血清肌酐、血尿素氮、血浆亚硝酸盐/硝酸盐水平、血清肿瘤坏死因子-α、肾组织匀浆丙二醛、超氧化物歧化酶和前列腺素 E2 水平升高。长期预防性给予α-TOL 可改善肾功能障碍和所有测量的氧化应激和炎症参数。脊髓缺血再灌注损伤引起了一些远程肾功能障碍,尽管一些观察到的变化可能是由于手术期间低血压引起的肾血流量减少所致。预防性长期给予α-TOL 可防止肾功能障碍,这种作用至少部分归因于改善肾促氧化剂/抗氧化剂平衡和抑制炎症过程。

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