Abstract：To investigate the possible role of peroxisome proliferators-activated receptor γ/uncoupling protein 2(PPARγ/UCP2) in learning and memory impairment induced by formaldehyde(FA), C57BL/6 mice were randomly divided into different groups including control group, T0070907group(inhibitor group), 3mg/m3 FA group, 3mg/m3 FA+T0070907 group. After 21 days of continuous exposure to FA or other treatments in the experiment, mouse brain tissue was taken to determine brain index and before being homogenized for the detection of a series of physiological indices such as reactive oxygen species(ROS), glutathione(GSH), malondialdehyde(MDA), nuclear factor κB(NF-κB), interleukin-6(IL-6), PPARγ, UCP-2, as well as the determination of pathological changes by observing the Nissl stained brain tissue. The results showed that compared with those of mice in the control group, the cerebral cortex neurons of the mice were damaged in the T0070907group and the 3mg/m3 FA group, the content of GSH decreased, and the levels of ROS, MDA, NF-κB, and IL-6 increased, with even more severe results were found in mice from the 3mg/m3 FA+T0070907 group. In addition, compared with the control group, the contents of PPARγ and UCP2 decreased in the brain tissue of mice in the T0070907 group, while increased in those from the 3mg/m3 FA group; compared with those of mice from the 3mg/m3 FA group, the contents of PPARγ and UCP2 decreased in the brain tissue of mice from the 3mg/m3 FA+T0070907 group after the inhibitor was administered. The content of PPARγ/UCP2 decreased after addition of T0070907, the inhibitor of PPARγ, which aggravated the learning and memory impairment in mice induced by FA exposure, therefore PPARγ/UCP2 may be protective to mice from the learning and memory impairment induced by FA.
郑丽芳, 萧嘉莉, 袁佩昕, 陈泊岐, 梅琼, 池煜瑶, 吕柯, 李睿. PPARγ/UCP2在甲醛致学习记忆障碍中的作用[J]. 中国环境科学, 2021, 41(6): 2923-2931.
ZHENG Li-fang, XIAO Jia-li, YUAN Pei-xin, CHEN Bo-qi, MEI Qiong, CHI Yu-yao, LV Ke, LI Rui. Role of the PPARγ/UCP2 in learning and memory impairment induced by formaldehyde. CHINA ENVIRONMENTAL SCIENCECE, 2021, 41(6): 2923-2931.
Tang X, Bai Y, Duong A, et al. Formaldehyde in China:Production, consumption, exposure levels, and health effects[J]. Environment International, 2009,35(8):1210-1224.
Zhang L, Steinmaus C, Eastmond A, et al. Formaldehyde exposure and leukemia:A new meta-analysis and potential mechanisms[J]. Mutation Research/reviews in Mutation Research, 2009,681(2/3):150-168.
韩华忠.甲醛暴露对职业工人外周血淋巴细胞微核率影响的研究[D]. 上海:复旦大学, 2012. Han H Z. Study on the effect of Formaldehyde exposure on the micronucleus formation in peripheral blood lymphocytes in professional workers[D]. Shanghai:Fudan University, 2012.
史利克,刘燕,王世博,等.病理科室内甲醛浓度的实时监测分析[J]. 化学工程与技术, 2018,8(1):37-40. Shi L K, Liu Y, Wang S B, et al. The analysis of Formaldehyde real-Time monitoring results in the Pathology Department[J]. Hans Journal of Chemical Engineering and Technology, 2018,8(1):37-40.
Takigawa T, Horike T, Ohashi Y, et al.. Were volatile organic compounds the inducing factors for subjective symptoms of employees working in newly constructed hospitals?[J]. Environmental Toxicology, 2010,19(4):280-290.
Liu X, Zhang Y, Wu R, et al. Acute formaldehyde exposure induced early Alzheimer-like changes in mouse brain[J]. Toxicol Mech Methods, 2018,28(2):95-104.
Kilburn, Kaye H. Neurobehavioral Impairment and Seizures from Formaldehyde[J]. Archives of Environmental Health:An International Journal, 1994,49(1):37-44.
王小玲.甲醛对小鼠中枢神经系统毒性的研究[D]. 山西:山西医科大学, 2008. Wang X L. Study on the toxicity of formaldehyde to the central nervous system of mice[D]. Shanxi:Shanxi Medical University, 2008.
Bhatt R, Singh P, John J, et al. Oxidative damage mediated iNOS and UCP-2upregulation in rat brain after sub-acute cyanide exposure:dose and time-dependent effects[J]. Drug & Chemical Toxicology, 2019,42(6):577-584.
Huang J, Liu W, Doycheva D, et al. Ghrelin attenuates oxidative stress and neuronal apoptosis via GHSR-1α/AMPK/Sirt1/PGC-1α/UCP-2pathway in a rat model of neonatal HIE[J]. Free Radical Biology and Medicine, 2019,141:322-337.
Almanza J, Alarcon F, Blancas G, et al. Glycine regulates inflammatory markers modifying the energetic balance through PPAR and UCP-2[J]. Biomedicine and Pharmacotherapy, 2010,64(8):534-540.
孙月丽,吴明玮,曾昭蕾,等.PPAR-γ抑制剂T0070907对人鼻咽癌细胞的生长抑制作用[J]. 中山大学学报(医学科学版), 2010,31(3):343-349. Sun Y L, Wu M W, Zeng Z L, et al. Growth inhibition of a selective PPAR-γ inhibitor, T0070907, in Nasopharyngeal Carcinoma Cells[J]. Journal of Sun Yat-sen University (Medical Science Edition), 2010, 31(3):343-349.
路雨,李瑶,胡赢丹,等.邻苯二甲酸二异癸酯对小鼠学习记忆的影响[J]. 中国环境科学, 2018,38(1):361-368. Lu Y, Li Y, Hu Y D, et al. Effects of Di-iso-decyl phthalate on the learning-memory ability in mice[J]. China Environmental Science, 2018,38(1):361-368.
Mahboubi A, Koushik A, Siemiatycki J, et al. Assessment of the effect of occupational exposure to formaldehyde on the risk of lung cancer in two Canadian population-based case-control studies[J]. Scandinavian journal of work Environment & Health, 2013,39(4):401-410.
Zhang L, Freeman L, Nakamura J, et al. Formaldehyde and leukemia:epidemiology, potential mechanisms, and implications for risk assessment[J]. Environmental & Molecular Mutagenesis, 2010,51(3):181-191.
Ye X, Ji Z, Wei C, et al. Inhaled formaldehyde induces DNA-protein crosslinks and oxidative stress in bone marrow and other distant organs of exposed mice[J]. Environmental and Molecular Mutagenesis, 2013,54(9):705-718.
Diaz R. Minireview:translational animal models of human menopause:challenges and emerging opportunities[J]. Endocrinology, 2012, 153(8):3571-3578.
Huang J, Lu Y, Zhang B, et al. Antagonistic effect of epigallocatechin-3-gallate on neurotoxicity induced by formaldehyde[J]. Toxicology, 2019,412:29-36.
李小琼,詹剑,冯赞杰,等.金钗石斛多糖减轻大鼠脑缺血再灌注损伤[J]. 中成药, 2017,39(4):677-683. Li X Q, Zhan J, Feng Z J, et al. Dendrobium nobile polysaccharides reduce cerebral ischemia reperfusion injury in rats[J]. Chinese Traditional Patent Medicine, 2017,39(4):677-683.
乔晓婷. 乳化剂吐温80对C57BL/6J小鼠毒性损伤作用[D]. 湖北:武汉轻工大学, 2016. Qiao X T. Toxic damage of emulsifier Tween 80 on C57BL/6J mice[D]. Hubei:Wuhan Polytechnic University, 2016.
鲁娴娴,黄佳伟,崔海燕,等.低浓度甲醛和PM2.5联合暴露对哮喘小鼠的影响[J]. 中国环境科学, 2020,40(3):1335-1344. Lu X X, Huang J W, Cui H Y, et al. The effect of combined exposure of low concentration formaldehyde and PM2.5 on asthma model mice[J]. China Environmental Science, 2020,40(3):1335-1344.
安洁然,江清英,李福宏,等.诱导型Hsp70在外源性甲醛对小鼠肝肾氧化损伤中的保护作用[J]. 生态毒理学报, 2019,14(2):222-230. An J R, Jiang Q Y, Li F H, et al. Inducible Hsp70 Protected liver and kidney of mice from the oxidation damage induced by exogenous formaldehyde[J]. Asian Journal of Ecotoxicolog, 2019,14(2):222-230.
陆林洁,蔡洁,安洁然,等.甲醛与DEHP联合染毒对小鼠学习记忆能力的影响[J]. 中国环境科学, 2017,37(12):4751-4762. Lu L J, Cai J, An J R, et al. Joint toxic effect of formaldehyde and DEHP on learning and memory of mice[J]. China Environmental Science, 2017,37(12):4751-4762.
Sorg B, Tschirgi M, Swindell S, et al. Repeated Formaldehyde Effects in an Animal Model for Multiple Chemical Sensitivity[J]. Annals of the New York Academy of Sciences, 2010,933:57-67.
曹杉杉.PPARγ在缺血预处理及其减轻后续缺血性脑损伤中作用机制的初步探讨[D]. 天津:天津医科大学, 2018. Cao S S. A preliminary study on the mechanism of PPARγ in ischemic preconditioning and its alleviation of subsequent ischemic brain injury[D]. Tianjin:Tianjin Medical University, 2018.
宋楠,秦川. PPARγ在阿尔茨海默病中的作用及影响因素研究进展[J]. 医学研究生学报, 2015,(9):989-994. Song N, Qin C. The role of PPARγin Alzheimer's disease and its impact factors[J]. Journal of Medical Postgraduates, 2015,(9):989-994.
abůRek M, JežEk J, JežEk P. Cytoprotective activity of mitochondrial uncoupling protein-2 in lung and spleen[J]. Febs Open Bio, 2018,8(4):692-701.
Ibrahim W, Tofighi R, Onishchenko N, et al. Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo[J]. Toxicology & Applied Pharmacology, 2013,269(1):51-60.
戎嵘.大豆异黄酮通过激活PPARγ抑制人乳腺癌MCF-7细胞增殖的作用研究[D]. 重庆:第三军医大学, 2011. Rong R. Study on the effect of soybean isoflavones on inhibiting the proliferation of human breast cancer MCF-7 cells by activating PPARγ[D]. Chongqin:Third Military Medical University, 2011.
赵精咪.谷氨酸兴奋毒性损伤对PPARγ表达及活性调节的体内研究[D]. 天津:天津医科大学, 2020. Zhao J M. Study on the regulation of PPARγ expression and activity by excitotoxic injury of glutamate in vivo[D]. Tianjin:Tianjin Medical University, 2020.
Mukhopadhyay D, Chattopadhyay A. Induction of oxidative stress and related transcriptional effects of sodium fluoride in female zebrafish liver[J]. Bulletin of Environmental Contamination and Toxicology, 2014,93(1):64-70.
Zhao X, Wang S, Wu Y, et al. Acute ZnO nanoparticles exposure induces developmental toxicity, oxidative stress and DNA damage in embryo-larval zebrafish[J]. Aquatic Toxicology, 2013,136:49-59.
Kawahara A, Haraguchi N, Tsuchiya H, et al. Peroxisome Proliferator-Activated Receptorγ (PPARγ)-Independent Specific Cytotoxicity against Immature Adipocytes Induced by PPARγ Antagonist T0070907[J]. Biological and Pharmaceutical Bulletin, 2013,36(9):1428-1434.
种莉,唐鹏,刘鹏,等.激活PPAR-γ对缺氧诱导的N9小胶质细胞迁移和炎症因子释放能力的影响[J]. 中华神经医学杂志, 2017, 16(1):40-45. Zhong L, Tang P, Liu P, et al. Role of peroxisome proliferator-activated receptor-γ in secretion of inflammatory cytokine and migration of N9 microglia cells induced by hypoxia[J]. Chinese Journal of Neuromedicine, 2017, 16(1):40-45.
Li S, Shi M, Wan Y, et al. Inflammasome/NF-κB translocation inhibition via PPARγ agonist mitigates inorganic mercury induced nephrotoxicity[J]. Ecotoxicology and Environmental Safety, 2020, 201:110801.