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槲皮素通过ROS介导的丝裂原活化蛋白激酶(MAPKs)和核因子κB(NF-κB)信号通路对铅诱导的大鼠肾脏炎症反应的保护作用。

Protective role of quercetin against lead-induced inflammatory response in rat kidney through the ROS-mediated MAPKs and NF-κB pathway.

作者信息

Liu Chan-Min, Sun Yun-Zhi, Sun Jian-Mei, Ma Jie-Qiong, Cheng Chao

机构信息

School of Life Science, Jiangsu Normal University, No.101, Shanghai Road, Tangshan New Area, Xuzhou City 221116, Xuzhou City, Jiangsu Province, PR China.

出版信息

Biochim Biophys Acta. 2012 Oct;1820(10):1693-703. doi: 10.1016/j.bbagen.2012.06.011. Epub 2012 Jun 21.

DOI:10.1016/j.bbagen.2012.06.011
PMID:22728154
Abstract

BACKGROUND

Lead (Pb) exposure is considered as a risk factor for the development of renal dysfunction. The flavonoid quercetin (QE) in diets exerts the nephroprotective effects. This study investigated the effects of quercetin on renal oxidative stress and inflammation in rats exposed to Pb.

METHODS

Wistar rats were divided into normal, lead exposure groups, lead plus quercetin groups and quercetin groups. Rats were exposed to lead acetate in the drinking water (500mgPb/L) with or without quercetin co-administration (25 and 50mgQU/kg intragastrically once daily). After 75days, serum uric acid, urea, creatinine, renal reactive oxygen species (ROS) production, thiobarbituric acid reactive substances (TBARS) and histopathological analysis were performed. Pb content in kidney was also assayed. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), the extracellular-receptor kinases (ERK1/2), the c-Jun N-terminal kinases (JNK1/2), p38 MAPK and nuclear factor-κB (NF-κB) were measured.

RESULTS

Quercetin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators and histopathological analysis. Quercetin significantly decreased Pb content in kidney. Pb-induced profound elevations of oxidative stress in kidney were suppressed by quercetin. Furthermore, quercetin significantly inhibited Pb-induced inflammation in rat kidney.

CONCLUSIONS

These results suggest that quercetin has the nephroprotective actions. The inhibition of Pb-induced kidney inflammation by quercetin is due at least in part to its anti-oxidant activity and its ability to modulate the MAPK and NF-κB signaling pathway.

GENERAL SIGNIFICANCE

Quercetin might be a potent nephroprotective drug to protect Pb-induced kidney injury.

摘要

背景

铅(Pb)暴露被认为是肾功能障碍发生的一个风险因素。饮食中的类黄酮槲皮素(QE)具有肾脏保护作用。本研究调查了槲皮素对铅暴露大鼠肾脏氧化应激和炎症的影响。

方法

将Wistar大鼠分为正常组、铅暴露组、铅加槲皮素组和槲皮素组。大鼠饮用含醋酸铅的水(500mgPb/L),同时或不同时给予槲皮素(25和50mgQU/kg,每日一次灌胃)。75天后,检测血清尿酸、尿素、肌酐、肾脏活性氧(ROS)生成、硫代巴比妥酸反应性物质(TBARS)并进行组织病理学分析。还检测了肾脏中的铅含量。测量肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、环氧化酶-2(COX-2)、细胞外受体激酶(ERK1/2)、c-Jun氨基末端激酶(JNK1/2)、p38丝裂原活化蛋白激酶和核因子-κB(NF-κB)的水平。

结果

槲皮素以剂量依赖的方式显著预防了铅诱导的肾毒性,这在诊断指标和组织病理学分析中均有体现。槲皮素显著降低了肾脏中的铅含量。槲皮素抑制了铅诱导的肾脏氧化应激的显著升高。此外,槲皮素显著抑制了铅诱导的大鼠肾脏炎症。

结论

这些结果表明槲皮素具有肾脏保护作用。槲皮素对铅诱导的肾脏炎症的抑制作用至少部分归因于其抗氧化活性及其调节丝裂原活化蛋白激酶和核因子-κB信号通路 的能力。

一般意义

槲皮素可能是一种有效的肾脏保护药物,可保护铅诱导的肾损伤。

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