慢性氟中毒大鼠脑组织中过氧化物酶体增殖物激活受体γ表达改变与氧化应激的关系  

Correlation between expression of peroxisome proliferator-activated receptor γ and oxidative stress in brains ofrats with chronic fluorosis

作　　者：刘仙红 陈丹 曾晓晓 葛启迪 谢春 董阳婷 邓婕[1] 官志忠 Liu Xianhong;Chen Dan;Zeng Xiaoxiao;Ge Qidi;Xie Chun;Dong Yangting;Deng Jie;Guan Zhizhong(Key Laboratory of Endemic Diseases and Minority Diseases of Ministry of Education, Guiyang 550004, Chin;Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang550004, Chin;Department of Environmental Hygiene, School of Public Health, Guizhou Medical University, Guiyang 550004, Chin)

机构地区：[1]地方病与少数民族疾病教育部重点实验室,贵阳550004 [2]贵州医科大学附属医院病理科,贵阳550004 [3]贵州医科大学附属医院公共卫生学院环境卫生学教研室,贵阳550004

出　　处：《中华地方病学杂志》2018年第6期450-454,共5页Chinese Journal of Endemiology

基　　金：国家自然科学基金(81760571);贵州省科技项目(黔教合协同创新中心[2014]06、黔科合重大专项 [2014]6008、黔科通[2016]161);教育部创新团队计划(IRT13058)

摘　　要：目的 研究慢性氟中毒神经损伤大鼠过氧化物酶体增殖物激活受体γ（PPARγ）的表达改变，探讨其与氧化应激水平 的关系。方法 健康纯系SD大鼠60只，体质量为100 - 120 g，按体质量采用随机数字表法分为对照组（饮水氟含量 〈 0.5 mg／L） 、低氟组（饮水氟含量为5.0 mg／L）、高氟组（饮水氟含量为50.0 mg／L），每组20只，雌雄各半，染氟时间分别为3和6个月。 染氟结束后，收集各组大鼠24 h 尿液；处死大鼠，取脑组织，采用氟离子选择电极法测定大鼠尿氟及脑氟含量；蛋白质免疫印迹 法（Western blot）和实时荧光定量PCR（Real-time PCR）法分别检测大鼠脑组织中PPARγ 蛋白和mRNA表达水平；黄嘌呤氧化酶 法和硫代巴比妥酸法测定大鼠血清超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量，并分析PPARγ蛋白表达与SOD及MDA的相关关系。结果 染氟3和6个月，低氟组大鼠尿氟及脑氟含量［（1.57 ± 0.18）mg／L、（3.43 ± 0.70）μg／g，（1.79 ± 0.17） mg／L、（7.40 ± 1.21）μg／g］高于对照组［（1.11 ± 0.17）mg／L、（2.39 ± 0.50）μg／g，（1.02 ± 0.15）mg／L、 （2.87 ± 0.82）μg／g，P均 〈 0.05］，且高氟组［（1.91 ± 0.23）mg／L、（6.70 ± 0.87）μg／g，（2.44 ± 0.51）mg ／L、（12.10 ± 1.30）μg／g］明显高于低氟组（P均 〈 0.05）。染氟3个月，高氟组大鼠脑组织海马及皮质的PPARγ 蛋白［（ 79.00 ± 3.46）%、（80.35 ± 2.50）%］及mRNA［（79.11 ± 11.18）%、（82.10 ± 9.94）%］表达均低于低氟组［（104.01 ± 5.77）%、（101.17 ± 6.35）%，（112.88 ± 22.15）%、（101.14 ± 8.60）%，P均 〈 0.05］；染氟6个月，高氟组大鼠脑 组织海马及皮质的PPARγ 蛋白［（64.32 ± 10.43）%、（60.20 ± 10.92）%］及mRNA［（41.03 ± 9.93）%、（52.25 ± 11.48）%］表达低于对照组［（99.99 ± 11.19）%、（100.00 ± 11.30）%，（100.00 ± 10.00）%Objective To detect the expression of peroxisome proliferator-activated receptor γ （PPARγ） in the brains of rats with chronic fluorosis and elucidate the relationship between PPARγ and oxidative stress in chronic fluorosis. Methods According to body weight （100 - 120 g）, sixty healthy SD rats were divided into control group（less than 0.5 mg/L fluoride in drinking water）, low fluoride group （5.0 mg/L fluoride in drinking water, prepared by NaF）, and high fluoride group （50.0 mg/L fluoride in drinking water） via the random number table method, 20 rats in each group （half male and half female）. The experiment periods were 3 and 6 months, respectively. Then 24-hour urine samples of rats were collected from each group, all rats were put to death and brain tissues were taken. The fluoride contents in urine and brain tissue were measured with fluoride-ion selective electrode; the levels of PPARγ protein and mRNA in the cortex and hippocampus were determined by Western blotting and Real-time fluorescence quantitative PCR, respectively; and the activities of superoxide dismutase （SOD） and level of malondialdehyde （MDA） in serum were detected by xanthine oxidase method and thiobarbituric acid method; the correlation between PPARγ protein expression and oxidative stress was analyzed. Results After 3 and 6 months of treatment, the contents of fluoride in urine and brain in low fluoride group [（1.57 ± 0.18） mg/L, （3.43 ± 0.70） μg/g; （1.79 ± 0.17） mg/L, （7.40 ± 1.21） μg/g] were higher than those of control group [（1.11 ± 0.17） mg/L, （2.39 ± 0.50） μg/g; （1.02 ± 0.15） mg/L, （2.87 ± 0.82） μg/g, P 〈 0.05], and the values in high fluoride group [（1.91 ± 0.23） mg/L, （6.70 ± 0.87） μg/g; （2.44 ± 0.51） mg/L, （12.10 ± 1.30） μg/g] were significantly higher than those in low fluoride group （P 〈 0.05）. In high fluoride group after 3 months of treatment, the expression of PPARγ protein [（79.00 ± 3.46）%, （80.35 ± 2.50）%]

关 键 词：氟 脑 过氧化物酶体增殖物激活受体Γ 超氧化物歧化酶 丙二醛 大鼠 

分 类 号：R599.1[医药卫生—内科学]