慢性砷暴露对小鼠肾组织DNA损伤的研究

目的:通过检测8-羟基脱氧鸟嘌呤(8-OHdG)在砷暴露小鼠肾脏组织中的表达和分布,探讨砷的肾毒性作用机制。方法:昆明种小鼠40只,随机分为4组,每组10只,分别为低剂量组(1ppmAs2O3)、中剂量组(2ppm As2O3)、高剂量组(4ppm As2O3)和生理盐水对照组,连续染毒60天后断头处死,用HE染色法进行组织病理学观察,用免疫组化及图像分析方法检测肾组织内8-OHdG的水平。结果:与对照组相比,1ppm、2ppm和4ppm染砷组小鼠肾组织出现不同程度细胞肿胀,胞浆空泡变性,核固缩、溶解及血管扩张、充血等病理学改变,近曲小管较肾小球损伤严重。免疫组化结果表明,肾组织中8-OHdG含量明显增高,并呈现明显的剂量-反应关系,其总光密度值与对照组比较具有显著性差异(P<0.01)。而且,8-OHdG在近曲小管的表达明显高于肾小球区域。结论:慢性低剂量砷暴露可引起小鼠肾组织DNA的氧化损伤和病理变化,尤其对肾脏近曲小管的损伤作用较为明显。

DNA damage in kidney tissue of mice exposed to arsenic with low dose

Objective:To explore the mechanism of arsenic toxicology to kidney by examining the expression of 8-hydroxy-2'-desoxyguanosine(8-OHdG).Methods:Forty mice were divided into 3 experimental groups and one controls.1 ppm As2O3,2 ppm As2O3 and 4 ppm As2O3 were administered ad libitum in water for consecutive 60 days,respectively,followed by decollation.Kidney tissues were taken and performed with HE staining and 8-OHdG expression were examined by immunohistochemistry.Results:The kidney cells in experimental groups showed swelling,vacuolation,nuclear breakage,lysis,vasodilation and congestion.Proximal convoluted tubules were more severe damaged than glomeruli.8-OHdG were also strongly expressed in these experimental groups.Conclusions:Kidneys showed severe pathologic injuries and DNA oxidative damage after long-term exposure to arsenic with low dose.The proximal convoluted tubules may be an main target of arsenic toxicity to kidneys.