慢性砷暴露人群血清差异表达蛋白研究  

Differential expression of serum proteins in chromic arsenic exposed population

作　　者：赵丽军[1] 高彦辉[1] 李媛媛[1] 冯红旗[1] 魏玮[1] 丁云鹏[1] 孙殿军[1] 

机构地区：[1]哈尔滨医科大学中国疾病预防控制中心地方病控制中心卫生部病因流行病学重点实验室、黑龙江省教育厅病因流行病学重点实验室,150081

出　　处：《中国地方病学杂志》2012年第1期7-12,共6页Chinese Jouranl of Endemiology

基　　金：“十一五”科技支撑计划课题（2006BA106B04）

摘　　要：目的 筛选慢性砷暴露人群血清差异表达蛋白,为寻找慢性砷暴露和砷中毒的血清蛋白标志物提供线索.方法 在山西省饮水型地方性砷中毒病区村进行现场调查,收集调查对象的人口学基本特征、饮水砷暴露史、吸烟、饮酒和健康情况等信息.根据饮水水砷浓度分组：低砷组（水砷暴露＜ 10μg/L）、中砷组（水砷暴露10 ～ 50 μg/L）、高砷组（水砷暴露＞50 μg/L）、砷中毒组（过去水砷暴露＞50 μg/L,改水后目前水砷＜10μg/L）,选择符合入组条件的调查对象,每组30例.砷中毒组诊断依据《地方性砷中毒诊断标准》（WS/T 211-2001）进行.根据知情同意的原则,采集4组人群静脉血,取血清,采用双向差异凝胶电泳（two-dimensional differential gel electrophoresis,2-D DIGE）筛选不同水砷浓度暴露组及砷中毒组血清差异表达蛋白,采用质谱进行蛋白鉴定.结果 在6张胶图中平均检测出蛋白点（1299±167）个,其中在5张胶中均出现的蛋白点有688个.在低、中、高砷组,有33个蛋白点存在差异表达（P＜ 0.01）；在低、中、高砷、砷中毒组,有54个蛋白点存在差异表达（P＜0.01）.对其中的25个蛋白点进行了质谱鉴定,成功的鉴定出13种蛋白.与低砷组比较,载脂蛋白A-Ⅳ、血浆视黄醇结合蛋白、雌激素受体（下丘脑亚型）在中、高砷组表达下调,补体4A和4B表达上调；与低、中、高砷组比较,β2糖化蛋白Ⅰ、角蛋白1、血红素结合蛋白前体、补体C1r亚单位、纤维凝胶蛋白3在砷中毒组表达下调,色素上皮衍生因子、α1-微球蛋白、羧肽酶N端催化链表达上调.结论 慢性砷暴露对人群血清蛋白产生显著影响,砷中毒人群血清中出现的差异表达蛋白不会在短期内随着饮水砷浓度的下降而全部得到改善,鉴定的差异表达蛋白能否作为慢性砷暴露或砷中毒的血清标志物还有待于进一步验证.Objectives To screen the differentially expressed proteins in serum of population chronically exposed to arsenic in drinking water,thus to provide candidate protein biomarkers for arsenic exposure and arsenicosis.Methods Subjects were selected from the drinking water type of endemic arsenicosis areas in Shanxi province,China.Demographic characteristics,history of arsenic exposure,cigarette smoking,alcohol drinking,health and other information were collected using questionnaire.The subjects were divided into low-arsenic group （with arsenic in drinking water 〈 10 μg/L）,medium-arsenic group（ 10 - 50 μg/L）,high-arsenic group（ 〉 50 μg/L）,and arsenicosis group（the drinking water with arsenic 〉 50 μg/L was replaced by low arsenic water 〈 10 μg/L）.The number of cases in each group was 30.The arsenicosis patients were diagnosed according to “Standard of Diagnosis for Endemic Arsenism” （WS/T 211-2001 ）.With the principle of informed consent,blood samples were collected.Differentially expressed serum proteins of different arsenic exposure groups and arsenicosis group were screened by two-dimensional differential gel electrophoresis（2-D DIGE）,and further identified by mass spectrometry （MS）.Results An average of （1299 ± 167） protein spots were identified in 6 gel images and 688 protein spots were discovered repeatedly in at least 5 gels.There were 33 protein spots differentially expressed among low-,medium- and high-arsenic groups P 〈 0.01）.Fifty four protein spots were significantly different among low-,medium-,high-arsenic exposure groups and arsenicosis group（P 〈 0.01 ）.Twenty five protein spots were selected for MS analysis,and 13 protein spots were identified.Compared with low-arsenic group,the expressions of apolipoprotein A-Ⅳ,retinol binding protein,and estrogen receptor hypothalamic isoform in medium- and higharsenic exposure groups were down regulated,and the expressions of component 4A and 4B were up regulated.Compared with low-,medium- and high-arsenic

关 键 词：砷 环境暴露 易伤人群 血清蛋白 双向差异凝胶电泳 质谱分析法 

分 类 号：R599[医药卫生—内科学]