燃煤污染型氟中毒人群DNA甲基转移酶1mRNA转录及蛋白表达  

DNA Methylation Transferase 1 Transcription and Protein Expression in Peripheral Blood of Patients with Endemic Fluorosis Induced by Coal Burning

作　　者：廖玉丹[1] 周金[1] 邱冰 廖永芳 严威敏 张爱华[1] 潘雪莉[1] 

机构地区：[1]贵阳医学院公共卫生学院卫生毒理学教研室,贵州550004 [2]贵州省骨科医院,贵州550004

出　　处：《环境与职业医学》2014年第12期941-943,共3页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金项目(编号:81260418);贵州省优秀科技教育人才省长基金项目(编号:黔省专合字[2011]54号)

摘　　要：[目的]了解燃煤污染型氟中毒人群外周血中DNA甲基化转移酶1(DNA methylation transferase 1,DNMT1)m RNA转录及蛋白表达情况,探讨其在氟中毒致病机制中的作用。[方法]在知情同意原则下,采集贵州省燃煤污染型氟中毒病区某县的调查对象尿液样本,采用氟离子电极法测定尿氟含量并依据尿氟含量将调查对象(380例)分为正常尿氟(尿氟<1.96 mg/g Cr)组(140例)、低氟(1.96 mg/g Cr≤尿氟<3.92 mg/g Cr)组(93例)、中氟(3.92 mg/g Cr≤尿氟<7.84 mg/g Cr)组(82例)、高氟(尿氟≥7.84 mg/g Cr组(65例);采用实时荧光定量PCR(FQ-PCR)法检测外周血中DNMT1 m RNA转录;采用酶联免疫吸附(ELISA)法检测外周血中DNMT1蛋白表达。[结果]调查对象外周血中DNMT1 m RNA转录,各组间差异具有统计学意义(F=3.125,P<0.05);进一步两两比较分析发现,低、中氟组DNMT1 m RNA转录高于正常尿氟组(P<0.05),且低氟组DNMT1 m RNA转录高于中、高氟组(P均<0.05)。调查对象外周血中DNMT1蛋白表达,各组间差异有统计学意义(F=3.113,P<0.05);进一步两两比较分析发现,低氟组DNMT1蛋白水平高于正常尿氟组(P<0.05),且低氟组DNMT1蛋白水平高于高氟组(P<0.05)。[结论]DNMT1参与氟中毒的发生发展过程,其转录及蛋白表达增强可能是氟骨症发生的早期分子事件。[ Objective ] To investigate the DNA methylation transferase 1 （DNMT1） transcription and protein expression in peripheral blood of patients with endemic fluorosis induced by coal burning, and explore the role of DNMT1 in fluorosis pathogenesis. [ Methods ] Following the principle of informed consent, urine samples were collected from 380 individuals residing in a coal-burning endemic fluorosis area of Guizhou. Urinary fluorine （UF） content was determined by fluoride ion selective electrode, according to which the investigated individuals were stratified into normal （UF〈1.96mg/gCr, 140 cases）, low （1.96mg/gCr ≤ UF〈3.92 mg/gCr, 93 cases）, medium （3.92 mg/gCr ≤F〈7.84 mg/gCr, 82 cases）, and high UF groups （UF ≥ 7.84 mg/gCr, 65 cases）. The mRNA transcription of DNMT1 was detected by real-time fluorescent quantitative polymerase chain reaction （FQ-PCR）. The DNMT1 protein was detected by enzyme linked immune sorbent assay （ELISA）. [ Results ] The transcription levels of DNMT1 mRNA in respondents＇ peripheral blood samples significantly varied among the groups （F=3.125, P 〈 0.05）. The results of pair- wise comparison found that the low and middle UF groups presented higher expression of DNMT1 mRNA transcription than the normal UF group （P〈 0.05）; the low UF group also showed higher expression of DNMT1 mRNA transcription than the medium and high fluoride exposure groups （P 〈 0.05）. The contents of DNMT1 protein in respondents＇ peripheral blood samples were different among the groups （F=3.113, P 〈 0.05）. The results of pair-wise comparison showed that the low UF group presented higher DNMT1 protein content than the normal UF group and the high UF group （P〈0.05）. [ Conclusion ] The elevated DNMT1 expression of its transcription and protein is involved in the fluorosis pathogenesis and could be early molecular events of fluorosis.

关 键 词：氟中毒 DNA甲基化 DNA甲基化转移酶1 m RNA转录表达 蛋白表达 

分 类 号：R114[医药卫生—卫生毒理学]