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白藜芦醇对甘油诱导的肾损伤的影响。

Effects of resveratrol on glycerol-induced renal injury.

作者信息

de Jesus Soares Telma, Volpini Rildo A, Francescato Heloísa D C, Costa Roberto S, da Silva Cleonice G A, Coimbra Terezila M

机构信息

Department of Physiology, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, São Paulo, 14049-900, Brazil.

出版信息

Life Sci. 2007 Aug 2;81(8):647-56. doi: 10.1016/j.lfs.2007.06.032. Epub 2007 Jul 24.

Abstract

Glycerol-induced renal lesions can have many causes, including increased oxidative stress and inflammation. Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, is an antioxidant agent with anti-inflammatory effects. In the present study, we investigated the possible protective effect of resveratrol on glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8 ml/kg of either 50% glycerol (n=18), glycerol+resveratrol (n=22), 0.15 M saline (n=14), saline+carboxymethylcellulose (n=10) or saline+resveratrol (n=8). The rats were killed 3 days after the injections, at which time the kidneys were removed for histological and immunohistochemical studies and lipid peroxidation determination. Blood and urine samples were collected in order to quantify sodium and creatinine. The results of the histological and immunohistochemical studies were scored according to the extent of damage and immunostaining, respectively, in the cortical tubulointerstitium. Lipid peroxidation was estimated by measuring malondialdehyde in renal tissue samples collected from control rats and glycerol-injected rats. By postinjection day 3, glycerol-only treated rats presented increases in plasma creatinine levels, as well as in fractional excretion of sodium and potassium (P<0.001). These increases were less pronounced in glycerol+resveratrol-treated rats (P<0.05). Cortical expression of macrophages, lymphocytes, nuclear factor-kappa B, heme oxygenase-1 and nitrotyrosine was greater in glycerol-treated rats than in controls (P<0.001). In addition, the histological findings for glycerol-treated rats were characteristic of acute tubular necrosis. Resveratrol attenuated all of these alterations (P<0.001). We conclude that resveratrol ameliorates glycerol-induced renal injury by suppressing the inflammatory process and by inhibiting lipid peroxidation.

摘要

甘油诱导的肾损伤可能有多种原因,包括氧化应激增加和炎症。白藜芦醇是一种在葡萄和红酒中发现的多酚类植物抗毒素,是一种具有抗炎作用的抗氧化剂。在本研究中,我们调查了白藜芦醇对甘油诱导的肾毒性可能的保护作用。将雄性Wistar大鼠肌肉注射8 ml/kg的50%甘油(n=18)、甘油+白藜芦醇(n=22)、0.15 M生理盐水(n=14)、生理盐水+羧甲基纤维素(n=10)或生理盐水+白藜芦醇(n=8)。注射后3天处死大鼠,此时取出肾脏进行组织学和免疫组化研究以及脂质过氧化测定。采集血液和尿液样本以定量钠和肌酐。组织学和免疫组化研究结果分别根据皮质肾小管间质的损伤程度和免疫染色进行评分。通过测量从对照大鼠和注射甘油的大鼠收集的肾组织样本中的丙二醛来估计脂质过氧化。到注射后第3天,仅用甘油处理的大鼠血浆肌酐水平以及钠和钾的分数排泄增加(P<0.001)。这些增加在甘油+白藜芦醇处理的大鼠中不太明显(P<0.05)。甘油处理的大鼠中巨噬细胞、淋巴细胞、核因子-κB、血红素加氧酶-1和硝基酪氨酸的皮质表达高于对照组(P<0.001)。此外,甘油处理的大鼠的组织学表现为急性肾小管坏死的特征。白藜芦醇减轻了所有这些改变(P<0.001)。我们得出结论,白藜芦醇通过抑制炎症过程和抑制脂质过氧化来改善甘油诱导的肾损伤。

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