小鼠衰老对不同组织中亚精胺的影响

Effects of Senescence on Endogenous Spermidine in Different Tissues of Mice

目的:本研究以模式小鼠C57BL为对象,研究小鼠在衰老过程中不同组织器官内源性亚精胺含量的变化。方法:利用高效液相色谱检测小鼠心脏和肝脏组织中亚精胺含量,进一步应用qRT-PCR以及Western blot检测在衰老过程中,不同组织器官中亚精胺生物合成途径的关键基因表达变化,利用亚精胺处理细胞检测DNA损伤应答能力。结果:随着衰老的发生心脏(199.09±17.12)和肝脏组织(168.92±5.12)中亚精胺含量显著降低,分别为78.01±13.52、62.05±6.73,差异有统计学意义(P<0.05);不同组织器官中亚精胺生物合成途径的关键基因Odc、Srm、Amd1的表达随衰老的发生明显下调,并且伴随着DNA损伤应答障碍;利用亚精胺处理细胞,能够增强细胞对DNA损伤的应答反应。结论:衰老的小鼠中内源性亚精胺含量降低,并且其合成途径的关键基因转录水平降低,导致细胞对DNA损伤应答能力减弱,从而加速机体衰老进程。

Objective： In this study, we examined the effects of senescence on endogenous spermidine of mice by model C57BL.Methods： The content of endogenous spermidine in heart and liver tissues was detected by high performance liquid chromatography（HPLC）. The expression pattern of key regulator genes in synthesis and metabolic pathways of spermine and DNA damage response was observed by RT-PCR and Western blotting, respectively. Results： The results showed that the contents of spermidine in heart and liver were decreased from 199.09±17.12 and 168.92±5.12 to 78.01±13.52 and 62.05±6.73, respectively. The difference was statistically significant（P〈0.05）. Further, qRT-PCR and Western blot have showed that the expression of key regulator genes in synthesis and metabolic pathways of spermine was were significantly down-regulated in different tissues at the process of senescence, and accompanied by DNA damage response impaired. Conclusions： With the occurrence of aging, endogenous spermidine was decreased, and the transcription level of key genes in synthesis and metabolic pathways were down-regulated, leading to DNA damage respond impaired and accelerated aging.