血管平滑肌细胞5-羟色胺受体1B差异表达影响手臂振动病发生的核因子-κB信号机制研究

项目名称： 血管平滑肌细胞5-羟色胺受体1B差异表达影响手臂振动病发生的核因子-κB信号机制研究

项目编号： No.81202183

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 陈青松

作者单位： 广东省职业病防治院

项目金额： 23万元

中文摘要： 手传振动接触广泛、危害严重，手臂振动病(HAVS)缺乏有效治疗手段，预后差。现有研究主要通过流行病学和动物实验探讨其影响因素和生物标志物，尚缺乏深入探讨其发生机制的细胞模型和方法。我们前期发现5-羟色胺1B受体(5-HT1B)基因5'端(2000bp)和编码区单核苷酸位点多态性与手传振动的损伤效应关联。本研拟进一步增加样本量以确认上述关联性，并分析人群中不同频率5-HT1B编码基因HTR1B 5'端(2000bp)单体型，研究其调控转录的功能活性差异，进而构建具有不同5-HT1B受控表达水平的人血管平滑肌细胞模型。通过这一细胞模型探讨5-羟色胺对平滑肌细胞增殖、分化、迁移，表面α2C肾上腺素和内皮素受体表达的影响以及氧化应激损伤差异的核因子-κB机制，并通过振动动物模型和人群血样分析相关指标验证上述机制。这将为在细胞和分子水平明确手臂振动病发生机制提供基础和依据。

中文关键词： 手臂振动病；5-羟色胺受体 1B；单体型分析；;核因子-κ B；炎症

英文摘要： Hand-transmitted vibration widely exists in occupational activities,which brings severe hazards to human health and may lead to Handarm Vibration Syndrome (HAVS),which is hard to remedy and almost irreversible.Previous epidemiological and in vivo animal experiment studies focused on exploration of the influencing factors,biomarkers and analysis of elementary mechanisms of HAVS.We have found that several Single Nucleotide Polymorphisms (SNPs) which are in the 5'flanking and coding region of 5-hydroxytryptamine receptor 1B (HTR1B) gene are associated with HAVS susceptibility.Based on what we found previously, we intend to analyze and screen haplotypes in the 5'flanking region that differ in regulating HTR1B expression,with which we will further construct different restructuring plasmids and then achieve cell models of which the 5-HT1B expression could be regulated.This project consists of animal experiments,epidemiological studies and cell models studies.How and to what extent the effects of diversity levels of 5-HT1B expression on vascular smooth muscle cells(SMC) proliferation,differentiation and the ability of withstand oxidant stress will be studied.Whether serotonin could activate NF-κB in SMC will be confirmed and We will unveil whether nuclear factor-κB pathway plays a crucial role in the progression of HAV

英文关键词： Hand-arm vibration syndrome；serotonin receptor 1B；haplotyping；NF-κ B；inflammation