动物造模 z-bio 2022-07-20 301

　　OBJECTIVE: To study the effects of simulated rapid altitude hypoxia on some physiological indexes and the expressions of MDR1 and MRP2 efflux drug transporters in the small intestine, liver and kidney of rats, and to preliminarily explore the effect of high altitude hypobaric hypoxia on drug transporters.

　　Methods: Wistar rats were randomly divided into normal control group, 24 h hypoxia group, and 72 h hypoxia group. Abdominal main venous blood was collected to analyze physiological indexes; Real-Time PCR was used to detect the expression levels of MDR1 and MRP2 transporter genes in different tissues of rats in each group; meanwhile, ELISA method was used to determine the protein expression changes of MDR1 and MRP2.

　　RESULTS: The results of physiological indicators showed that the rats in the simulated hypoxia group had obvious changes compared with the normal control group. Compared with the normal control group, the expression of MDR1 and MRP2 genes in the small intestine, liver and kidney of the hypoxia group was significantly increased, and the protein level was also increased (P<0.05, P<0.01), but with the prolongation of hypoxia time , different transporters have different trends in different organs and tissues.

　　CONCLUSION: High altitude hypoxia can cause changes in physiological indexes and the expressions of MDR1 and MRP2 in rapidly advancing rats, which in turn affect the disposition of the above-mentioned transporter substrates in vivo, which can provide a theoretical basis for the study of high altitude pharmacokinetics.