Effect of hypoxia on expressions of MDR1 and MRP2 in rats / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To study the changes in the physiological parameters and gene expression of two drug efflux transporters MDR1 and MRP2 in the small intestine, liver and kidney of rats exposed to acute hypoxia.</p><p><b>METHODS</b>Eighteen Wistar rats were randomly divided into control group, hypoxia for 24 h group and hypoxia for 72 h group. Blood samples were obtained from the abdominal aorta of the rats after the exposure for analyzing the physiological indexes. The mRNA expressions of MDR1 and MRP2 were determined using Real-Time PCR, and their protein expressions were detected with enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The physiological parameters of the rats in hypoxia group were significantly changed compared with those in the control group. The expressions of MDR1 and MRP2 mRNA and proteins in the small intestine, liver and kidney were significantly increased in rats with hypoxic exposure than in the control rats (P<0.05 or 0.01). As the hypoxic exposure prolonged, the two transporters showed different patterns of variation in different tissues.</p><p><b>CONCLUSION</b>Acute hypoxia affects the physiological parameters and expression levels of MDR1 and MRP2, thus causing changes in the metabolism of the substrates of the transporters. These changes may play an important role in the pharmacokinetics of drugs at a high altitude.</p>