目的 探讨商陆水煎液致大鼠肾损伤特点及毒性机制。方法 大鼠随机分为商陆高剂量组(20 g生药·kg-1·d-1)、低剂量组(10 g生药·kg-1·d-1)和对照组,连续灌胃给药或纯水49 d,停药恢复7 d。于不同时间点处理动物,收集血液样本;全自动生化仪检测血清血尿素氮和肌酐。称动物体重与各组织质量,计算各组织脏器指数。取肾脏分别进行HE/PAS/Masson染色,光镜下观察肾脏组织病理学改变。试剂盒法检测肾组织中超氧化物歧化酶活性、丙二醛含量、谷胱甘肽过氧化酶活力、一氧化氮含量。结果 与对照组比,血尿素氮在高、低剂量组分别于第21、49天显著升高;肌酐在高、低剂量组均于第35天显著升高,有一定的时-量-效关系。组织病理学观察到该药致肾损伤表现主要为肾小管上皮嗜碱性变、间质纤维化和蛋白管型。与对照组比,高剂量组肾组织超氧化物歧化酶/丙二醛和谷胱甘肽过氧化酶活性降低,一氧化氮含量升高,提示肾组织过氧化物增多,脂质过氧化反应增强。结论 长期给予大剂量商陆水煎液可引起大鼠肾损伤,其机制可能与氧化应激反应有关。
Abstract
OBJECTIVE To explore characteristics and mechanism of renal injury caused by giving Radix Phytolaccae(RP) decoction in rats. METHODS Rats were divided into three groups:normal control, high and low dose of RP groups which were administrated respectively with pure water or equal volume of RP at the doses of 20, 10 g穔g-1 daily by gavage for consecutive 49 d, and observed continually for 7 d after drug withdrawal. Blood sample was collected at different time points. The contents of serum blood urea nitrogen (BUN)and creatinine (CR)were detected by automatic biochemical analyzer. The body and tissue weight were both weighed. The rations of every tissue weight to body weight were counted,respectively. HE, PAS or Masson stain were used in the slices of kidney samples at each treatment time point,and the renal histopathological changes were observed under light microscopy. The activity of superoxide dismutase(SOD), glutathione peroxidase(GSH-px)and the contents of malon dialdehyde(MDA), nitric oxide(NO)in kidney samples were measured with Kits.RESULTS Compared with those in the control group, BUN in low dose group was significantly increased on day 49, BUN in high dose group was significantly increased on day 21,CR in low and high dose group were both significantly increased on day 35,with a time-dose-effect relationship. The renal histopathological change was characterized by renal tubular epithelial cell degeneration, necrosis, shedding, tubulointerstitial fibrosis and protein cast. Compared with those in the control group, the activity of GSH-px, and the ratio of SOD/MDA in the kidney were significantly decreased in high dose group, the tissue content of NO was increased, indicating that there was an increase of peroxide and lipid peroxidation in kidney. CONCLUSION The renal injury caused by giving high dose of RP decoction in rats in a long period of time may be related to oxidative stress reaction.
关键词
商陆 /
肾损伤 /
机制 /
氧化应激
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Key words
Radix Phytolaccae /
renal injury /
mechanism /
oxidative stress
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中图分类号：
R965
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参考文献
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脚注
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基金
国家“重大新药创制”科技重大专项资助项目(2009ZX09502-002);国家重点基础研究发展计划(973计划)(2009CB522807)
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