环境低砷暴露地区2型糖尿病...细胞相对端粒长度的关系研究_李洪娅.pdf

1 2 5CARCINOGENESIS，TERATOGENESIS&MUTAGENESIS论著癌变畸变突变2023 年 3 月第 35 卷第 2 期收稿日期：2023-01-14；修订日期：2023-02-28基金项目：国家自然科学基金（81872661，81472998）作者信息：李洪娅，E-mail：；#并列第一作者，廖清华，E-mail：。*通信作者，赵志强，E-mail：；何云，E-mail：环境低砷暴露地区2型糖尿病人群尿砷水平与外周血单个核细胞相对端粒长度的关系研究李洪娅1，廖清华2，#，付浩祥2，肖柏香3，苏珩1，谢易容1，刘洁仪1，魏青1，王凤1，皮姝荣1，陈福彬1，赵志强4，*，何云1，*(1中山大学公共卫生学院毒理学教研室，广东广州510080；2广东韶州人民医院，广东韶关512000；3南昌大学附属眼科医院，江西南昌330006；4广东省职业病防治院毒理实验所，广东广州510080)Relationships between urinearsenic levels and relativetelomere length in bloodmononuclear cells among type-2diabetic patients exposedto low levels of arsenicLI Hongya1,LIAO Qinghua2,#,FU Haoxiang2,XIAO Baixiang3,SU Heng1,XIE Yirong1,LIU Jieyi1,WEI Qing1,WANG Feng1,PI Shurong1,CHEN Fubin1,ZHAO Zhiqiang4,*,HE Yun1,*(1.Department of Health Toxicology,School of Public Health,Sun Yat-senUniversity,Guangzhou 510080,Guangdong;2.Guangdong ShaozhouPeoples Hospital,Shaoguan 512000,Guangdong;3.Affiliated EyeHospital of Nanchang University,Nanchang 330006,Jiangxi;4.Institute ofToxicology,Guangdong Province Hospital for Occupational DiseasePrevention and Treatment,Guangzhou 510080,Guangdong,China)【摘要】目的：探讨环境低砷暴露地区2型糖尿病人群尿砷浓度与外周血单个核细胞(PBMC)相对端粒长度的关系。方法：选取华南某地574名2型糖尿病患者作为研究对象，进行基本情况调查与生化指标检测，利用电感耦合等离子质谱仪(ICP-MS)检测尿砷浓度，实时荧光定量PCR法(qPCR)检测PBMC相对端粒长度。根据尿砷浓度将研究对象分为3组，比较各组间生化指标与PBMC相对端粒长度的差异；采用单因素与多因素有序Logistic回归分析研究2型糖尿病人群PBMC相对端粒长度的影响因素；采用SPSSProcess 2.0分析糖化血红蛋白在尿砷与相对端粒长度之间的中介效应。结果：2型糖尿病患者尿砷中位数为29.80 g/L，四分位数间距为39.81 g/L。PBMC相对端粒长度为0.820.60，低砷组、中砷组与高砷组PBMC相对端粒长度分别为1.040.92，0.770.29与0.630.28，差异具有统计学意义(P0.05)。多因素有序Logistic回归分析发现，尿砷是影响相对端粒长度的危险因素；中砷组与低砷组相比，OR(95%CI)为2.149(1.451，3.182)；高砷组与低砷组相比，OR(95%CI)为4.077(2.687，6.185)，差异均具有统计学意义(P0.01)。中介效应分析结果显示，尿砷对相对端粒长度的直接效应值为-0.287(-0.369，-0.204)，糖化血红蛋白是尿砷与相对端粒长度之间的一个中介变量，中介效应值为-0.072(-0.106，-0.045)，中介比例为19.99%。结论：环境低砷暴露条件下，尿砷是影响2型糖尿病患者PBMC相对端粒长度的危险因素，尿砷浓度越高，相对端粒长度越短。2型糖尿病患者PBMC相对端粒长度可能是砷暴露的潜在生物标志。【关键词】相对端粒长度；尿砷；2型糖尿病；低水平砷暴露中图分类号：R587.1文献标志码：A文章编号：1004-616X(2023)02-0125-07doi：10.3969/j.issn.1004-616x.2023.02.008【ABSTRACT】OBJECTIVE：Toexplorerelationshipsbetweentherelativetelomerelengthofbloodmononuclear cells(PBMC)and urine arsenic concentration in type-2 diabetic patients exposed to low levels ofarsenic.METHODS：A total of 574 patients with type 2 diabetes in South China were selected as the studyobjects.Basic information was collected and biochemical indicators were detected.Urine arsenic concentrationswere detected using inductively coupled plasma mass spectrometer(ICP-MS)technology，and relative telomerelengths of PBMC were detected by real-time fluorescence quantitative PCR(qPCR)technology.The studysubjects were divided into 3 groups according to their urine arsenic concentrations.Differences of biochemical论著癌变畸变突变1 2 6CARCINOGENESIS，TERATOGENESIS&MUTAGENESISVol.35No.2Mar.2023indicators and PBMC relative telomere lengths among the 3 groups were compared.Single-and multi-factorordinal logistic regressions were used to analyze influencing factors for the relative telomere lengths.Themediating effects of Hemoglobin A1c(HbA1c)between urine arsenic levels and relative telomere lengths wereanalyzed using SPSS Process 2.0.RESULTS：The median urine arsenic level in the patients was 29.80 g/L，and the interquartile interval was 39.81 g/L，and the relative telomere length was 0.820.60.The relativetelomere length in low，medium and high arsenic groups were 1.04 0.92，0.77 0.29 and 0.63 0.28，respectively.Differences of relative telomere lengths among the three groups were statistically significant(P0.05).Multivariate ordinal logistic regression analyses showed that urine arsenic was a risk factor for relativetelomere length.Compared with the low arsenic group，the OR(95%CI)of the medium arsenic group was2.149(1.451，3.182)，and that of the high arsenic group was 4.077(2.687，6.185)，the differences werestatistically significant(P0.01).The direct effect value of urine arsenic on relative telomere length was-0.287(-0.369，-0.204).HbA1cwas a mediating variable between urine arsenic and relative telomere length，with themediatingeffectvaluebeing-0.072(-0.106，-0.045)andthemediatingproportionbeing19.99%.CONCLUSION：Presence of arsenic in urine is a risk factor for relative telomere length of PBMC in type-2diabetic patients：the higher the urine arsenic levels，the shorter the relative telomere lengths.The relativetelomere length of PBMC in these patients may be a potential biomarker for arsenic exposures.【KEY WORDS】relative telomere length；urine arsenic；type 2 diabetes；low level arsenic exposure端粒是位于真核细胞染色体末端的保护性结构，对染色体的稳定性和完整性非常重要，并会随着年龄的增长而缩短1。作为氧化应激的生物标志物2，端粒的磨损常因某些导致氧化应激的环境因素、职业暴露或慢性疾病而加剧3。2型糖尿病作为最常见的一种慢性代谢性疾病，有研究表明，端粒长度与2型糖尿病具有显著的相关性4-6。但研究结论尚不一致。砷作为公认的环境致癌物，与心血管疾病、癌症、糖尿病等疾病的发病风险相关7-8。目前关于砷与外周血单个核细胞(peripheral blood mononuclear cell，PBMC)端粒长度的关系多集中于研究高水平砷暴露人群，研究发现，在尼泊尔、阿根廷、孟加拉国与印度，砷暴露与端粒长度之间呈正相关9-12，而Borghini等13在意大利进行的一项研究却发现砷暴露与端粒长度之间呈边缘性负相关。环境低砷暴露地区2型糖尿病患者尿砷浓度是否是PBMC相对端粒长度的影响因素，2型糖尿病患者PBMC相对端粒长度是否可作为砷暴露的潜在生物标志，目前仍不清楚。本研究以华南某地2型糖尿病患者作为研究对象，旨在探讨环境低砷暴露地区2型糖尿病患者PBMC相对端粒长度与尿砷浓度的关系，为揭示环境低水平砷暴露对2型糖尿病患者PBMC端粒长度的影响提供线