【Animal Experiment】-The effect of hypoxia on the expression of drug transporters MDR1 and MRP2 in rats

  OBJECTIVE: To study the effects of simulated rapid hypoxia on the expression of several physiological indicators in rat small intestine, liver, kidney and high-altitude low-pressure drug transporters, as well as the secretion of MDR1 and MRP2 drug transporters. Preliminary study of the effects of hypoxia.

  Method: Wistar rats were randomly divided into a normal control group, a hypoxia group for 24 hours and a hypoxia group for 72 hours. Collect the main venous blood in the abdominal cavity for physiological index analysis. Real-time fluorescent quantitative PCR was used to detect the expression levels of MDR1 and MRP2 transporter genes in different tissues of each group of rats. At the same time, the protein expression changes of MDR1 and MRP2 were measured by ELISA.

  Results: The physiological index results show that rats in the simulated hypoxia group have significant 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 was significantly increased, and the protein level was also increased (P\u003c0.05, P\(u003c0.01) but lacked The oxygen time is prolonged, and different transporters have different trends in different organs and tissues.

  Conclusion: High altitude hypoxia may cause rapid development of rat physiological indicators and changes in the expression of MDR1 and MRP2, which may affect the in vivo processing of the aforementioned transporter substrates. Have. This provides a theoretical basis for the study of plateau pharmacokinetics.