姜黄素对镉致大鼠肾Nrf2及HO-1、γ-GCS、Gpx-1 mRNA和蛋白表达的影响  

Effect of curcumin on expressions of Nrf2、HO-1、γ-GCS and Gpx-1 in the kidney of rats exposed to cadmium

作　　者：黎珊珊[1] 徐兆发[1] 李静慧[1] 杨天瑶[1] 奉姝[1] 李乐慧[1] 刘巍[1] 

机构地区：[1]中国医科大学公共卫生学院环境卫生学教研室,辽宁沈阳110001

出　　处：《毒理学杂志》2015年第1期31-35,共5页Journal of Toxicology

摘　　要：目的探讨Nrf2及HO-1、γ-GCS、Gpx-1在镉所致肾脏氧化应激中的作用及姜黄素对其的影响。方法 Wistar大鼠32只按体重随机分为4组,每组4只,分别为对照组、低剂量Cd Cl2组、高剂量Cd Cl2组和姜黄素干预组。1~3组大鼠予皮下注射生理盐水,第4组大鼠给予皮下注射50 mg/kg姜黄素;2 h后,第1组仍腹腔注射生理盐水,第2~4组大鼠分别腹腔注射3、6和6μmol/kg Cd Cl2溶液,每周染毒5次,隔日干预1次,连续干预与染毒6周。采用流式细胞仪测定肾细胞内ROS水平,Real-time PCR和Western blotting法测定Nrf2、HO-1、γ-GCS、Gpx-1的mRNA和蛋白表达。结果与对照组比较,在高剂量Cd Cl2组中ROS含量,Nrf2、HO-1、γ-GCS的mRNA及蛋白表达均显著升高（P〈0.01）,Gpx-1的mRNA及蛋白表达显著降低（P〈0.01）。与高剂量Cd Cl2组比较,姜黄素干预组ROS含量显著降低,Nrf2、HO-1、γ-GCS、Gpx-1的mRNA及蛋白表达均显著升高（P〈0.01）。结论姜黄素可拮抗镉所致的大鼠肾脏氧化应激,其机制可能与Nrf2及其调控下游HO-1、γ-GCS和Gpx-1表达有关。Objective To study the effects of Nrf2、HO-1、γ-GCS and Gpx-1 on the nephrotoxicity in rats exposed to cadmiun and to observe the effects of curcumin on nephrotoxicity of cadmium. Methods Thirty-two Wistar rats were divided randomly into four groups by weight,they were control group,low-dose cadmium chloride group,the high-dose cadmium chloride group and curcumin intervention group.The rats in the first,second and third groups were injected subcutaneously with normal saline,while the rats in the fourth group were injected subcutaneously with 50 mg / kg curcumin. Two hours later,the first group was intrapentoneal injection with normal saline. The second,third and fourth groups were respectively given intrapentoneal injection of 3 μmol / kg,6 μmol / kg and 6 μmol / kg cadmium chloride. The curcumin pretreatment was given in 2 days interval,3 times a week,while cadmium chloride was given every day,5 times a week,all lasting for 6weeks. Renal cell ROS production was detected by flow cytometry analysis,the mRNA and protein expressions of Nrf2,HO-1,γ-GCS,Gpx-1 were determined with Real-time PCR and Western blotting methods. Results Compared with the control group,the level of ROS,the mRNA and protein expressions of Nrf2,HO-1,γ-GCS increased significantly（ P 〈 0. 01）; and the mRNA and protein expressions of Gpx-1decreased significantly in the high-dose cadmium chloride treated groups（ P 〈 0. 01）. Compared with the high-dose cadmium treated groups,the pretreatment group of curcumin could significantly decrease the ROS levels,the mRNA and protein expressions of Nrf2,HO-1,γ-GCS and increase the mRNA and protein expressions of Gpx-1（ P 〈 0. 01）. Conclusion Curcumin may present an antagonistic effect on renal damage induced by cadmium,and the primary mechanism may be related with the expressions of Nrf2,HO-1,γ-GCS and Gpx-1.

关 键 词：镉 姜黄素 核转录因子NF-E2相关因子2 活性氧 氧化应激 肾损伤 

分 类 号：R992[医药卫生—毒理学]