模拟失重对大鼠肝脏CYP1A2的影响研究

为揭示失重条件下药物代谢酶变化规律，考察了不同模拟失重周期对鼠肝代谢酶CYP1A2的影响.将大鼠尾悬吊3，7，14，21 d模拟失重效应，分别采用Western-blot、Q-PCR及HPLC-UV检测鼠肝微粒体中CYP1A2的蛋白表达、mRNA表达及活性变化.与对照组相比，模拟失重3 d大鼠肝脏CYP1A2的蛋白表达量显著下降（p<0.05），7，14 d显著上升（p<0.05），21 d略有下降（p>0.05）.在大鼠肝脏CYP1A2 mRNA量及活性方面，模拟失重3，7，14 d均显著上升（p<0.05），21 d上升不明显（p>0.05）.实验结果表明模拟失重14 d鼠肝中的CYP1A2蛋白、基因表达及活性显著上升，但21 d各指标有恢复到正常组的趋势. 

Effect of Simulated Microgravity on Hepatic CYP1A2 in Rats

To provide basic research data for understanding the changes of metabolic enzymes under weightlessness, the effect of simulated microgravity on hepatic CYP1A2 in rats was investigated. After the rats are tail suspended for 3, 7, 14 and 21 days, the protein expression, mRNA expression and the CYP1A2 activity were detected by western-blot, Q-PCR and HPLC-UV methods. Compared with the control group, the expression of CYP1A2 protein decreases significantly (p<0.05) in the 3 d tail suspended (TS) rats, but increases significantly (p<0.05) in the 7 and 14 d TS rats. The expression of protein decreases slightly (p> 0.05) in the 21 d TS rats. The mRNA expression and activity of CYP1A2 increase significantly (p<0.05) in 3, 7 and 14 d TS rats and increase slightly (p> 0.05) in 21 d TS rats compared with the control group. The 14 d simulated group has the most significant effect on the expression and the activity of hepatic CYP1A2 in rats. All the indices in 21 d TS rats show the tendency to the control group level. This study provides basic research data for understanding changes of metabolic enzymes and drug safety of astronauts under the microgravity condition.