癌变·畸变·突变2018，Vol.30Issue(1)：1-7,7.DOI:10.3969/j.issn.1004-616x.2018.01.001
硒对慢性镉暴露致大鼠肾损伤的保护作用与机制
Protective effect of selenium in chronic cadmium exposure-induced kidney injury in rats
摘要
Abstract
OBJECTIVE:To investigate the protective effect of selenium on toxicity of rat kidney injury caused by chronic cadmium exposure and its possible mechanism.MATERIALS:The forty-eight male SD rats were randomly divided into four groups:blank control,cadmium exposure,negative control,and selenium treatment groups.There were 12 rats in each group,and animals were given deionized water,cadmium chloride,sodium selenite,and coprocessing with cadmium chloride and sodium selenite by gastric gavage,respectively,for six days a week for twelve weeks.After treatment,blood,urine and kidney tissues were collected to determinate renal function indexes,such as urea nitrogen,creatinine,and total protein in serum and urine.We observed the pathological changes and detected level and/or activity of ROS (reactive oxygen species),MDA (malondialdehyde),T-SOD (total superoxide dismutase),and NAG (N-acetyl-beta-d-glucosidase) in renal tissue.The protein imprinting method was used to detect protein expression of SETD6,DJ-1,and Nrf2.RESULTS:Biochemical and pathological results show that cadmium induced renal injury in rats,caused glomerular swelling,generalized lesions of renal tubules,and renal interstitial congestion,inflammatory cell infiltration.The levels of ROS and MDA in the kidney tissues increased (P＜0.05),and activities of T-SOD decreased (P＜0.05),indicating that cadmium exposure induced oxidative stress injury in the renal tissue.However,after selenium intervention,the renal tissue structure and functional damage caused by cadmium exposure were reduced,indicating that selenium had protective effect on kidney injury caused by cadmium exposure.At the same time,compared with the blank control,SETD6,DJ-1 and Nrf2 showed varying degrees of reduced protein expression after cadmium exposure (P＜0.05).After selenium intervention,compared to cadmium exposure group,SETD6 protein expression was significantly downregulated (P＜O.05),DJ-1 and Nrf2 protein expression were significantly up-regulated (P＜0.05),kidney damage was reduced,suggesting that selenium might have played a protective role by inhibiting the expression of SETD6 and enhancing the expression of DJ-1 and Nrf2.CONCLUSION:Selenium effectively reduced the rat renal toxicity induced by chronic cadmium exposure.Its mechanism might be that under oxidative stress condition,selenium promoted the expression of DJ-1 by inhibiting SETD6,and thus upregulated the expression of antioxidant transcription factor Nrf2,through which enhanced the antioxidant capacity,and reduced the oxidative stress injury which was induced by cadmium exposure.关键词
硒/镉肾毒性/氧化应激/保护作用/机制Key words
selenium/cadmium nephrotoxicity/oxidative stress/protective effect/mechanism分类
医药卫生引用本文复制引用
周庆彪,刘颖,孔德钦,张佳欣,于卫华,柏桦,海春旭..硒对慢性镉暴露致大鼠肾损伤的保护作用与机制[J].癌变·畸变·突变,2018,30(1):1-7,7.基金项目
国家自然科学基金项目(81473010) （81473010）
陕西省自然科学基金项目(2016JM8024) （2016JM8024）
