一对糖尿病双生子病证结合调查及差异表达基因分析

Analysis of TCM Syndrome Patterns and Different Genes Expressions of Monozygotic Twin with Diabetes Mellitus

目的：以糖尿病双生子为模型,进行六纲（寒、热、表、里、虚、实）及脏腑辨证,以病证结合的方法探索糖尿病不同发展阶段中医证型分布特征及其与微观基因表达的关系。方法：首先,卵型鉴定处于患糖尿病不同发展阶段的双生子对;其次,采用158项的六纲调查量表和68项的肾虚量表评分不同时间段的肾虚证候;最后应用基因芯片技术,筛选这对单卵双生子之间的差异表达基因谱,并进行数据分析。结果：大双与小双这对双生子的六纲症状和肾虚证候积分存在着明显差异,小双的积分是大双的1.5～3倍。基因芯片结果发现有19条基因的表达值发生了明显的变化,其中与细胞生理程序、新陈代谢相关的基因表达均出现下调。讨论：双生子的病与证、宏观与微观结合研究是可行性的,双生子糖尿病与中医肾虚证具有相关性。基因芯片结果提示糖尿病肾虚证的发生与新陈代谢、细胞生理程序功能相关基因表达异常密切相关。

Objective： To explore the TCM symdrome pattern at different stages of diabetes mellitus and the relevance with differentially expressed genes using a monozygotic twin as model. Methods： A monozygotic female twin of 64 years old with diabetes were investigated according to two questionnaires of six guiding principles for diagnosis with 158 items and kidney-deficiency syndrome with 68 items. Their differentially expressed gene profiles were then obtained through DNA mieroarray test. Results ： In terms of the scores of six guiding principles and Kidney-deficiency syndrome, there was significant difference between the twin. The younger sister had a score 1.5 - 3 times of the elder sister. Nineteen bands of genes showed difference in the gene expression. Among which, 7 genes were up-regulated and 12 genes were down-regulated. Conclusion ： The occurrence and development of diabetes mellitus with kidney-difieieney is the interaction of multi-factors, including the most important genetic and environmental factors. Kidney-difieieney syndrome may be the main TCM pattern for the diabetes mullitus in this twin pair. Furthermore, those genes for metablism, cellular physiological process, and response to stimulus are all down-regulated, and those genes for cell communication are mixedly regulated. This may be the bio-moleeular background for diabetes mellitus.