Effects of hypoxia on the expression of drug transporters MDR1 and MRP2 in rats

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

  Method: Wistar rats were randomly divided into normal control group, hypoxia 24 h group, and hypoxia 72 h group. The main venous blood of the abdominal cavity was taken to analyze physiological indicators; Real-Time PCR method was used to detect the expression levels of MDR1 and MRP2 transporter genes in different tissues of rats in each group; at the same time, the protein expression changes of MDR1 and MRP2 were determined by ELISA method.

  Result: The physiological index results show that the simulated hypoxia group has obvious changes compared with the normal control group. Compared with the normal control group, the expression of MDR1 and MRP2 genes in the three tissues of the small intestine, liver and kidney of the hypoxia group increased significantly, and the protein level also increased (P<0.05, P<0.01), but with the prolonged hypoxia time , Different transporters have different trends in different organs and tissues.

  Conclusion: High altitude hypoxia can cause changes in the physiological indicators and the expression of MDR1 and MRP2 in rapidly advancing rats, and then affect the disposal of the above-mentioned transporter substrates in the body. This can provide a theoretical basis for plateau pharmacokinetic studies.