EF调控老年大鼠淋巴细胞基因表达谱中凋亡相关信号分子表达的研究

Regulation of apoptosis-related molecules in gene expression profile in old rats by Epimedium Flavonoids

目的揭示EF对老年大鼠淋巴细胞凋亡相关信号分子及通路的调节机制。方法利用基因芯片技术,并比较老年大鼠、青年大鼠、EF干预后的淋巴细胞基因表达。结果老年大鼠与青年大鼠比较,促进细胞凋亡作用的基因表达显著上调,具有抗凋亡作用的基因表达显著下调;具有抗增殖作用的基因表达显著上调,具有促进细胞增殖作用的基因表达显著下调;参与淋巴细胞活化增殖及免疫反应等基本信号通路的组成元件中,多个重要信号分子的表达显著下调。EF组抗淋巴细胞凋亡的几个上游因子如CD28、TGFβ及cJun、cFos、cMyc等癌基因显著上调;促细胞凋亡基因Caspase1、Caspase2、Caspase3、Caspase6、CalpainⅡ、CathepsinS、Dnaseγ、PKCdelta等表达显著下调;CathepsinB、Mtal、NFkappaB、Notch等抗凋亡基因表达显著上调。显著上调促细胞增殖基因PCNA、Araf、CyclinGassociatedkinase等的转录,显著下调抗增殖的Rb等基因的转录。显著上调免疫细胞效应及功能的基本调节因子CD2、CD3、CD5、TCR、IL2、IL2R(CD25)、CD28、CTLA4的表达。结论EF能上调老年大鼠淋巴细胞抗凋亡基因表达的同时,下调抗增殖基因的表达;上调促增殖基因表达的同时,下调抗增殖基因的表达,重塑基因表达良性平衡;还协同调节TCRCD3、CD28、CTLA4、TGFβ、IL2R等介导的?

Objective:To uncover the molecules and signal transduction underlying apoptosis in lymphocytes in old rats.Methods:The rats were grouped into three of old rats control,young rats control,EF-treated group,and studied the gene expression in genome-wide scale with genechip.Results:Compared to young rats control,pro-apoptotic genes were up-regulated and anti-apoptotic genes were down-regulated in old rats.And pro-proliferation genes were down-regulated,the anti-proliferation genes were regulated reversely.Furthermore,a number of genes involved in signal transduction in immune activation and immune response showed lower expression level.But in EF-treated group,pro-apoptotic genes such as Caspase1、Caspase2、Caspase3、Caspase6、CalpainⅡ、Cathepsin S、Dnase γ、PKCdelta,and anti-proliferation genes including Rb were predominantly down-regulated.Anti-apoptotic genes such as Cathepsin B、Mtal、NF-kappa B、Notch,and pro-proliferation genes including c-Fos、c-Myc、c-Jun、PCNA、A-raf;CyclinG-associated kinase were regulated reversely.Especially many genes mediating apoptosis signal including CD2、CD3、CD5、TCR、IL-2、IL-2R(CD25)、CD28、CTLA4 were up-regulated.Conclusion:By a novel mean including up-regulation of anti-apoptotic and down-regulation of pro-apoptotic gene expression,up-regulation of pro-proliration and down-regulation of anti-proliferation gene expression,the normal lymphocyte function in old rats was reconstructed.Additionally EF can coordinate TCR/CD3、CD28、CTLA4、TGFβ、IL-2R-mediated signal to reach its anti-apoptotic effects on lyphocytes in old rats. [