db/db糖尿病肾病小鼠肾脏基因表达谱及大黄酸对其的影响

Renal gene expression profiles of db/db mice and its alteration after the treatment with rhein

目的 :利用基因芯片技术了解db/db糖尿病小鼠肾脏基因表达谱及其经大黄酸治疗后的变化 ,进一步研究糖尿病肾病 (DN)的分子发病机制和大黄酸治疗DN的作用机制。 方法 :利用国际学术界公认的标准化Affymetrix公司生产的GM U74A基因芯片分别检测正常对照组 (db/m小鼠 )、DN组 (db/db小鼠 )、大黄酸治疗组 [大黄酸 15 0mg/ (kg·d)治疗 12周 ]肾脏基因表达谱 ,并利用生物信息学方法对检测结果进行分析。 结果 :分别得到了正常对照组、DN组、以及大黄酸治疗组的肾脏基因表达谱。分析发现 ,在总共 12 437个基因 (包括EST)中 ,与正常对照组相比 ,DN组有 10 85个基因表达下调 ,37个基因表达上调 ,其中变化幅度大于 2倍的分别有 16 6个和 2 9个 ;与DN组相比 ,大黄酸治疗组有 384个基因表达下调 ,15 5个表达上调 ,其中变化幅度大于 2倍的分别有 47个和 30个。结论 :利用基因芯片技术在阐明了DN肾脏基因的表达谱同时 ,证实大黄酸治疗可以改变其基因的表达谱 ,为进一步研究DN的分子发病机制和大黄酸治疗的作用机制创造了条件。

Objective:To explore the renal gene expression profiles of db/db mice and its alteration after treated with rhein,and to further investigate the molecular mechanism of diabetic nephropathy and of rhein therapeutic effect. Methodology:Eight weeks old diabetic db/db mice were treated with or without rhein at a dosage of 150 mg/(kg·d) for 12 weeks.The renal gene expression profiles were tested using the gene chip GM-U74A from Affymetrix company.The results were analyzed by bioinformatical method.The db/m mice were used as normal control. Results:Among the total 12 437 tested genes,the expressions of 1 085 genes were down-regulated and 37 genes were up-regulated in untreated db/db mice when compared with normal control.Among them,166 genes were down-regulated and 29 genes up-regulated more than 2 fold.It was found that 384 genes were down-regulated and 155 genes up-regulated in rhein treated db/db mice as compared with untreated db/db mice.And 47 genes were down-regulated and 30 genes up-regulated more than 2 fold. Conclusion:The renal gene expression profile of diabetic nephropathy in db/db mice has been explored and the candidate genes of rhein effect on diabetic nephropathy have been revealed using the gene chip technique in this study.