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大骨节病患者外周血真菌毒素环境反应基因表达谱的研究
Gene expression profile of mycotoxin-related environmental response genes in the peripheral blood in Kashin-Beck disease
【摘要】 目的比较分析真菌毒素环境反应基因在大骨节病(KBD)患者和正常对照者外周血中的表达谱差异,探讨其与KBD患病风险的相关性。方法收集25例KBD成年患者和17例正常对照个体外周血样品,提取总RNA。采用Agilent全基因组表达芯片、单基因表达分析和基因集富集表达分析技术(GSEA),比较真菌毒素环境反应基因在KBD患者和正常对照个体外周血中的基因表达谱差异。基因表达芯片数据采用RT-PCR进行验证。结果①T-2毒素、雪腐镰刀菌烯醇、玉米赤霉烯酮、脱氧镰刀菌烯醇、黄曲霉毒素B1、赫曲霉毒素A和胶霉毒素相关的11个环境反应基因在KBD患者和正常对照个体外周血中的表达水平存在显著差异(表达率>2.0或<0.5),功能主要涉及细胞凋亡、免疫炎症和蛋白合成与修饰等。②真菌毒素相关的11个环境反应基因在KBD患者外周血中显著上调(P<0.05),功能涉及细胞凋亡、外环境刺激反应、生长发育和氧化还原反应等。结论多种真菌毒素环境反应基因在KBD患者外周血中表达异常。真菌毒素可能通过影响相关环境反应基因的表达,诱发软骨细胞功能障碍,导致关节软骨损伤。
【Abstract】 Objective To compare the expression profile of mycotoxin-related environmental response genes(MERGs) in the peripheral blood of Kashin-Beck disease(KBD) patients and healthy controls so as to explore the relationship between MERGs and articular cartilage lesions in KBD.Methods Peripheral blood specimens were collected for total DNA from 17 normal human subjects and 25 adult KBD patients.Agilent whole genome microarray chip,single gene and gene set enrichment expression analyses were applied to compare the gene expression profile of MERGs between KBD and healthy controls.RT-PCR was performed to validate microarray data.Results ① Eleven MERGs related to T-2 toxin,nivalenol,deoxynivalenol,zearalenone,aflatoxin B1,ochratoxin A and gliotoxin presented significant differences of expression between KBD and healthy controls(ratios >2.0 or <0.5).The 11 MERGs were involved in various biological processes,mainly including apoptosis,immunity and inflammation as well as protein synthesis and modification.② Mycotoxin-related 11 MERGs ontology was significantly up-regulated(P<0.05) in the peripheral blood of KBD patients,and was involved in apoptosis,external environmental stimuli,growth and development as well as oxidation-reduction reaction.Conclusion Various MERGs have abnormal expressions in KBD patients,which may affect the function of chondrocytes and lead to articular cartilage lesions in KBD.
【Key words】 Kashin-Beck disease; mycotoxin; environmental response gene; microarray; peripheral blood;
- 【文献出处】 西安交通大学学报(医学版) ,Journal of Xi’an Jiaotong University(Medical Sciences) , 编辑部邮箱 ,2012年04期
- 【分类号】R684.1
- 【被引频次】4
- 【下载频次】263