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.