摘要
目的研究关木通水煎剂(AMK)致大鼠肾毒性及DNA损伤机制。方法用健康雄性SD大鼠经灌胃AMK(50 g/kg),并与对照组比较。观察指标有:肾组织形态学变化、体重、肾脏系数、血尿素氮(BUN)及肾皮质丙二醛(MDA)含量;采用彗星试验检测肾组织中的DNA链断裂程度;利用免疫组化检测8-羟基脱氧鸟苷(8-OHdG)表达情况。结果给药组动物的肾组织形态学变化、体重、肾脏系数、BUN及MDA含量等各项观察指标均有明显改变,与对照组比较差异有统计学意义(P<0.05)。彗星试验结果显示,AMK引起明显的DNA迁移,其中尾矩变化最明显。对照组、给药3、5及7 d组肾组织的彗星尾矩分别为1.52±1.10、12.77±16.05、97.97±17.85及111.77±16.65。给药组肾组织8-OHdG表达高于对照组。结论AMK经口给药50 g/kg连续3 d,即可引起肾损伤。AMK可致肾组织活性氧增高,进而引起DNA氧化性损伤,这可能与AMK的肾毒性有关。
Objective To study the nephrotoxicity of aristolochia manshuriensis kom （AMK） and possible mechanism of DNA damage in rats. Method Healthy male adult SD rats were given AMK through gavage （50 g/kg） and compared with control groups.The following indices were observed： histological changes, body weight, kidney index, contents of blood urea nitrogen （BUN） and malondialdehyde（MDA） in kidney. DNA strand-breaks were determined by comet assay. 8-hydroxy-2＇-deoxyguanosine（8-OHdG） were determined by immunohistochemical method. Results There were obvious change in the histological changes, body weight, kidney index, BUN and MDA of the rats that treated with AMK, which had significant difference compared with the control groups （ P 〈 0.05 ）. AMK caused a significant increase of the DNA migration, in which increased tail moment was the most obvious. The tail moments in control and AMK for 3,5 and 7 d were 1.52 ± 1.10,12.77 ± 16.05,97.97 ± 17.85 and 111.77 ± 16.65, respectively. The expression of 8-OHdG of kidney in AMK groups was intensified. Conclusion AMK,50 g/kg per day orally for 3 consecutive days, caused kidney damage in rats. AMK could increase the reactive oxygen species in kidney and therefore induce DNA damage. That could be relevant to the nephrotoxicity of AMK.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2007年第6期444-446,共3页
Journal of Toxicology
关键词
关木通
马兜铃酸
肾毒性
DNA损伤
8-OHDG
Aristolochia manshuriensis kom
Aristolochic Acid
Nephrotoxicity
DNA damage
8- Hydroxy-2＇-deoxyguanosine
