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氟化物对大鼠肝脏DNA损伤及半胱天冬酶介导的细胞凋亡的影响

Effects of Fluoride on DNA Damage and Caspase-Mediated Apoptosis in the Liver of Rats.

作者信息

Song Guo Hua, Huang Fu Bing, Gao Ji Ping, Liu Mao Lin, Pang Wen Biao, Li Wei bin, Yan Xiao Yan, Huo Mei Jun, Yang Xia

机构信息

Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Road Xinjian 56, Taiyuan, 030001, China,

出版信息

Biol Trace Elem Res. 2015 Aug;166(2):173-82. doi: 10.1007/s12011-015-0265-z. Epub 2015 Feb 20.

DOI:10.1007/s12011-015-0265-z
PMID:25693680
Abstract

Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver. In this study, we investigated liver histopathology, DNA damage, apoptosis, and the mRNA and protein expressions of caspase-3 and -9 in the rat livers by administering varying concentrations of fluoride (0, 50, 100, 200 mg/L ) for 120 days. The results showed fluoride-induced morphological changes and significantly increased apoptosis and DNA damage in rats exposed to fluoride, especially in response to higher doses. The immunohistochemical and qRT-PCR results indicated that caspase-3, caspase-9 protein positive expression and mRNA relative expression enhanced with increasing NaF concentration. In summary, our findings suggest that chronic exposure to fluoride causes damages to liver histopathology and leads to liver apoptosis through caspase-mediated pathways.

摘要

氟化物化合物在环境中含量丰富,以各种浓度广泛分布。此外,氟化物会在肝脏等靶器官中诱导毒性作用。在本研究中,我们通过给予不同浓度的氟化物(0、50、100、200mg/L)120天,研究了大鼠肝脏的组织病理学、DNA损伤、细胞凋亡以及caspase-3和-9的mRNA和蛋白质表达。结果表明,氟化物会诱导形态学变化,并显著增加暴露于氟化物的大鼠的细胞凋亡和DNA损伤,尤其是在高剂量时。免疫组织化学和qRT-PCR结果表明,随着NaF浓度的增加,caspase-3、caspase-9蛋白阳性表达和mRNA相对表达增强。总之,我们的研究结果表明,长期接触氟化物会导致肝脏组织病理学损伤,并通过caspase介导的途径导致肝脏细胞凋亡。

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