基于基因表达谱数据建立肾虚证量化数学模型

作者	单位
沈自尹	复旦大学附属华山医院中西医结合研究所
张新民	复旦大学附属华山医院中西医结合研究所
林伟	复旦大学数学系
吴斌	复旦大学附属华山医院中西医结合研究所
黄建华	复旦大学附属华山医院中西医结合研究所
刘小雨	复旦大学附属华山医院中西医结合研究所
许世雄	复旦大学力学工程系 (上海200040)

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中文摘要:

目的利用基因表达谱数据,建立量化肾虚证程度的数学模型。方法采用4、10、18、24月龄SD大鼠,以24月龄大鼠加淫羊藿总黄酮(EF)干预,摘取大鼠下丘脑、垂体、肾上腺、淋巴细胞、骨、肝、肾、脾,利用基因芯片技术,检测全基因组mRNA表达,用不同月龄大鼠的基因表达谱数据建立神经网络模型,然后用此模型评价EF干预肾虚证的效果。结果7个组织共筛选到199个基因表达具年龄依赖特征,其中相当一部分为神经内分泌免疫相关基因。模型预判发现EF作用后,24月龄老龄大鼠下丘脑、垂体、肾上腺、肝、肾、骨、脾的基因表达与8～13月龄大鼠相似,分别为12.64、10.87、8.10、12.70、11.93、13.14、10.13月龄。结论基于基因表达谱数据能建立量化肾虚证程度的模型,并能预测补肾药的效果,研究也表明EF能使老年状态基因表达向年轻化靠近,提示其具有改善肾虚、延缓衰老的作用。

英文摘要:

Objective To establish a quantitative mathematical model of Shen-deficiency syndrome of TCM by utilizing whole-genome transcriptional profiles.Methods The 4,10,18,24 months old SD rats were used,24-months aged rats intervened by Epimedium Flavonoids(EF)were adopted in the experiment.Rats’ hypothalamus,pituitary,adrenal,lymphocytes,bone,liver,and kidney,and spleen were taken for determining whole-genome mRNA expression with gene chip,and a quantitative nerve network model was established by utilizing the gene expression profile of different aged rats,then the model was used to evaluate the effects of EF on Shen-deficiency syndrome.Results Totally 199 genes showing age-dependent characteristics were screened out from the 7 kinds of tissue,most of them were neuro-endocrine immune related genes.Evaluation based on the mathematical model showed the age of hypothalamus,pituitary,adrenal,liver,kidney,bone,and spleen in the 24-months rats after EF intervention was 12.64,10.87,8.10,12.70,11.93,13.14,and 10.13 months,respectively.Conclusion A quantitative mathematical model can be established based on the gene expression profile,it is suitable for estimating the efficacy of Shen-tonifying drugs.EF can make the gene expression of elder close to the young state,suggesting that EF has action in improving Shen-deficiency syndrome and delaying senescence.

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