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特丁基对苯二酚对单侧输尿管梗阻诱导的雄性大鼠肾氧化应激、炎症和细胞凋亡的改善作用。

Ameliorating effect of troxerutin in unilateral ureteral obstruction induced renal oxidative stress, inflammation, and apoptosis in male rats.

机构信息

Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Khalije Fars Blvd., Pistachio Co. Street, 77175-835, Rafsanjan, 7719617996, Iran.

Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2020 May;393(5):879-888. doi: 10.1007/s00210-019-01801-4. Epub 2020 Jan 3.

DOI:10.1007/s00210-019-01801-4
PMID:31900517
Abstract

Unilateral ureteral obstruction (UUO) induces renal injury and troxerutin attenuates the inflammatory parameters and decreases oxidative stress. Accordingly, this study explored the renoprotective effect of troxerutin in UUO-induced renal oxidative stress, inflammation, and apoptosis in male Wistar rats. Animals were randomly separated into five groups (n = 8): control, UUO, and three UUO groups treated with troxerutin (1, 10, and 100 mg/kg). UUO-induced and vehicle/troxerutin administration was continued for 3 days. Then serum creatinine, mean arterial pressure (MAP), renal perfusion pressure (RPP), renal vascular resistance (RVR), and renal blood flow (RBF) were measured. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels as some oxidative stress parameters were measured in the left kidney. The immunoblotting method was applied to evaluate the cleaved caspase-3 Bax, Bcl-2, and TNF-α proteins level. The hematoxylin and eosin method was used to assess the kidney tissue damage score (KTDS). In 3 days, UUO significantly increased serum creatinine level, KTDS, RVR, MDA, Bax, cleaved caspase-3, and TNF-α protein levels (p < 0.05); and decreased RBF, TAC, SOD, catalase, GPx activity levels and Bcl-2 protein expression level in the left kidney (p < 0.05). Troxerutin (100 mg/kg) significantly attenuates the indicators alteration induced by UUO. Our findings represented that the renoprotective effect of troxerutin may be related to its anti-oxidative stress, anti-inflammation, anti-apoptosis, and RBF improver properties.

摘要

单侧输尿管梗阻 (UUO) 可导致肾脏损伤,而曲克芦丁可减轻炎症参数并降低氧化应激。因此,本研究探讨了曲克芦丁对 UUO 诱导的雄性 Wistar 大鼠肾脏氧化应激、炎症和细胞凋亡的保护作用。动物随机分为五组(n=8):对照组、UUO 组和曲克芦丁(1、10 和 100mg/kg)治疗的 UUO 组。UUO 诱导和载体/曲克芦丁给药持续 3 天。然后测量血清肌酐、平均动脉压 (MAP)、肾灌注压 (RPP)、肾血管阻力 (RVR) 和肾血流量 (RBF)。左肾中测量超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GPx) 和过氧化氢酶活性、总抗氧化能力 (TAC) 和丙二醛 (MDA) 水平等一些氧化应激参数。应用免疫印迹法评估裂解的 caspase-3 Bax、Bcl-2 和 TNF-α 蛋白水平。苏木精和伊红法用于评估肾组织损伤评分 (KTDS)。在 3 天内,UUO 显著增加血清肌酐水平、KTDS、RVR、MDA、Bax、裂解的 caspase-3 和 TNF-α 蛋白水平(p<0.05);并降低左肾中的 RBF、TAC、SOD、过氧化氢酶、GPx 活性水平和 Bcl-2 蛋白表达水平(p<0.05)。曲克芦丁(100mg/kg)显著减轻 UUO 引起的指标改变。我们的研究结果表明,曲克芦丁的肾脏保护作用可能与其抗氧化应激、抗炎、抗细胞凋亡和改善 RBF 有关。

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