pH值对FOXO1、GDF-8基因反义RNA寡核苷酸吸收的影响

The Influence of pH Value on the Absorption of RNA Interference Oligos of FOXO1 and GDF-8 Gene

研究不同pH值下,口服靶向FOXO1与GDF-8基因反义RNA寡核苷酸药物对药效的影响。化学合成靶向FOXO1与GDF-8基因的有效反义RNA寡核苷酸片段,调节药物PH值,通过灌胃方式给药,给药20 d后处死小鼠,进行体重,腿部肌肉增长情况分析。提取腿部肌肉组织总RNA,用real time PCR检测FOXO1与GDF-8基因的表达。结果表明,服用RNA oligos的试验组小鼠腿部肌肉重量均比对照组肌肉重量增长快。其中pH为7.0的RNA oligos的效果比pH为5.0的效果好,pH9.0的RNAoligos的作用效果最弱。与小鼠体重变化结果一致,real time PCR检测实验组FOXO1与GDF-8基因转录水平较对照组均有明显下降,其中服用pH为7.0的RNA oligos的下降最多。因此,口服靶向FOXO1与GDF-8基因的反义RNA寡核苷酸药物的最适pH值应为中性偏酸。

It was to evaluate the influence of pH value on the absorption of antisense RNA oligos targeted to FOXO1 and GDF-8. Antisense RNA oligos was synthesized to adjust the pH value of the dissolved RNA solution. After 20 days feeding, the body wight of mice and the muscle quality of thigh were analysized. Total RNAs from the thigh skeletal muscles were isolated and real time PCR analysis of FOXO1 and GDF-8 gene was done. Results showed that the mice fed effective RNA oligos had more thigh muscle mass compared with control group. Real time PCR results showed that the FOXO1 and GDF-8 gene transcription levels decreased rapidly compared with control groups. Thus, the most appropriate pH value for absorption of antisense RNA oligos targeted to FOXO1 and GDF-8 is acidity or neutral.