慢性氟中毒大鼠脑组织中依赖还原型辅酶/醌氧化还原酶1及血红素氧合酶1的表达  

Influence of chronic fluorosis on expression of quinone oxidoreductase-1 and heme oxygenase-1 in rat brains

作　　者：王娅[1] 董阳婷 魏娜[1] 官志忠[1] 

机构地区：[1]贵阳医学院病理教研室,550004

出　　处：《中华地方病学杂志》2015年第4期250-253,共4页Chinese Journal of Endemiology

基　　金：国家自然科学基金（81160335）;科技部国际合作重大项目（2013BA105B03）;贵州省科技厅国际合作项目（黔科合外G字[2011]7014号）

摘　　要：目的 观察慢性氟中毒大鼠脑组织中依赖还原型辅酶/醌氧化还原酶1 （quinone oxidoreductase-1,NQO1）和血红素氧合酶1（heme oxygenase-1,HO1）mRNA和蛋白表达水平的改变,以及对转录因子NF_E2相关因子2/抗氧化反应元件（Nrf2/ARE）信号通路的影响,探讨氟中毒性脑损伤的机制.方法 SD大鼠60只,采用随机数字表法,按照体质量分为对照组（饮水氟含量＜ 0.5 mg/L）、染氟组（饮水氟含量为50.0 mg/L）,每组30只,雌雄各半;实验期为10个月,观察氟斑牙情况,并收集大鼠24 h尿液;心脏灌流处死大鼠后,取后肢股骨和大脑组织.用氟离子选择电极法测定大鼠尿氟及骨氟;用蛋白印迹方法和实时荧光定量PCR分别检测脑组织中NQO1、HO1蛋白和mRNA表达水平.结果 染氟组大鼠出现不同程度的氟斑牙,对照组大鼠牙齿无异常改变;染氟组大鼠尿氟[（2.16±0.39）mg/L]及骨氟[（211.07±40.52）mg/kg]均高于对照组[（1.70±0.24）mg/L,（34.67±11.15）mg/kg,t=2.11、3.23,P均＜0.05].染氟组大鼠脑组织中NQO1、HO1蛋白表达[（255.2±14.3）％、（187.2±11.1）％]高于对照组[（100.0±12.2）％、（100.0±8.9）％,t=2.14、2.05,P均＜0.05].染氟组脑组织中NQO1、HO1 mRNA表达[（210.2±9.8）％、（154.5±7.4）％]高于对照组[（100.0±10.4）％、（100.0±9.7）％,t=2.33、2.75,P均＜0.05].结论 慢性氟中毒导致脑组织中NQO1及HO1表达水平升高,可能与Nrf2/ARE信号通路的开启有关,对代偿性增强细胞抗氧化能力有一定作用.Objective To investigate the changes of expression of quinone oxidoreductase-1 （NQO1） and heme oxygenase-1 （HO1） at protein and mRNA levels in the brains of rats with chronic fluorosis,effect on NF-E2-related factor 2/antioxidant response element （Nrf2/ARE） signal pathway,and reveal the mechanism of brain damage induced by the disease.Methods SD rats were randomly divided to two groups of 30 each （half females and half males）,e.g.the normal control group （drinking water containing less than 0.5 mg/L of fluorine） and fluoride exposed group （drinking water containing 50.0 mg/L sodium fluoride,NaF）.All rats were examined at the 10 months after feeding NaF.Dental fluorosis of rats was observed; the fluoride contents in urine and bone were detected by fluoride-ion selective electrode; protein and mRNA levels of NQO1 and HO1 in brains were detected by Western blotting and quantitative real timePCR,respectively.Results The dental fluorosis was observed,and contents of fluoride in urine [（2.16 ± 0.39）mg/L] and bone [（211.07 ± 40.52）mg/kg] determined in the rats of the fluoride group were higher than those of controls [（1.70 ± 0.24）mg/L,（34.67 ± 11.15）mg/kg,t =2.11,3.23,all P〈 0.05].The protein expression levels of NQO1 and HO1 in the brains of rats with fluorosis [（255.2 ± 14.3） % and （187.2 ± 11.1）%] were also higher than those of controls [（100.0 ± 12.2）%,（100.0 t 8.9）%,t =2.14,2.05,all P 〈 0.05]; the mRNA levels of NQO1 and HO1 [（210.2 ± 9.8）% and （154.5 ± 7.4） %] in the rats of the fluoride group were increased as compared to those of controls [（100.0 ± 10.4）%,（100.0 ± 9.7）%,t =2.33,2.75,all P 〈 0.05].Conclusion The expression of NQO1 and HO1 in brain of rats with fluorosis are significantly increased,which may be due to the activation of Nrf2/ARE signal pathway and may play a compensative role in enhancing antioxidant ability.

关 键 词：氟中毒 大鼠 脑 依赖还原型辅酶/醌氧化还原酶1 血红素氧合酶1 

分 类 号：R599.1[医药卫生—内科学]