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探讨高原低氧对药物代谢酶CYP2C9、2C19活性和蛋白表达的影响。平原、中度海拔急性缺氧、中度海拔慢性缺氧、高海拔急性缺氧和高海拔慢性缺氧等5组大鼠分别灌胃给予探针药物苯妥英钠(PHT)和奥美拉唑(OMZ),采用RP-HPLC法分别测定给药后12 h血清中苯妥英钠和代谢产物4’-羟基苯妥英(HPPH)以及3 h血清中奥美拉唑和代谢产物5-羟基奥美拉唑(5-OHOMZ)的血药浓度,以HPPH与PHT的浓度比值评价CYP2C9的活性,以5-OHOMZ与OMZ的浓度比值评价CYP2C19的活性。采用ELISA方法测定CYP2C9和2C19的蛋白表达。与平原对照组大鼠比较,中度海拔急性缺氧组、中度海拔慢性缺氧组、高海拔急性缺氧组和高海拔慢性缺氧组大鼠CYP2C9的活性和蛋白表达均无显著性变化。与平原对照组大鼠比较,中度海拔急性缺氧组、中度海拔慢性缺氧组、高海拔急性缺氧组和高海拔慢性缺氧组大鼠CYP2C19的蛋白表达无显著性变化,但高海拔急性缺氧组大鼠CYP2C19的活性显著升高,其他组无显著性变化。研究结果提示,高原低氧对CYP2C19的活性有一定影响。
To investigate the effect of plateau hypoxia on the activity and protein expression of CYP2C9,2C19. Five groups of rats in the plains, middle altitude acute hypoxia, middle altitude chronic hypoxia, high altitude acute hypoxia and high altitude chronic hypoxia were administered with phenytoin sodium (PHT) and omeprazole OMZ). The concentrations of phenytoin and metabolites 4’-hydroxyphenytoin (HPPH) and omeprazole 3-h serum and 5-hydroxy-omeprazole 5-OHOMZ) were used to evaluate the activity of CYP2C9 in the ratio of the concentration of HPPH to PHT. The activity of CYP2C19 was evaluated by the ratio of 5-OHOMZ to OMZ. The protein expression of CYP2C9 and 2C19 was determined by ELISA. Compared with the plain control group, the activity and protein expression of CYP2C9 in moderate altitude acute hypoxia group, moderate altitude hypoxia group, high altitude hypoxia group and high altitude hypoxia group had no significant change . Compared with the plain control group, the protein expression of CYP2C19 in moderate altitude acute hypoxia group, moderate altitude hypoxia group, high altitude acute hypoxia group and high altitude hypoxia group had no significant change, but high The activity of CYP2C19 in rats with acute hypoxia at altitude was significantly increased, but no significant changes in other groups. The results suggest that high altitude hypoxia CYP2C19 activity to some extent.