中文摘要：

目的探讨高原低氧对大鼠肝脏中药物转运体MDR1、MRP1、BCRP蛋白及mRNA表达的影响。方法SD大鼠随机分为七组：平原对照组和中度海拔急性缺氧组、中度海拔慢性缺氧组、高度海拔急性缺氧组、高度海拔慢性缺氧组、中海拔慢性缺氧返回西宁组、高海拔慢性缺氧返回西宁组。采用ELISA和实时定量PCR法分别测定MDR1、MRP1、BCRP蛋白和mRNA的表达。结果与平原组相比，MDR1的蛋白表达在其他六组的大鼠肝脏显著降低了16．3％、27．3％、27．3％、33．1％、39．0％、41．3％；MDR1的mRNA表达在其他六组的大鼠肝脏显著降低了33．0％、34．0％、48．1％、47．2％、48．1％、52．8％；MRP1在肝脏中的蛋白表达显著降低了19．4％、31．7％、34．0％、50．9％、52．0％、56．0％；MRP1在肝脏中的mRNA表达显著降低了18．9％、23．4％、36．9％、30．6％、27．0％、29．7％；BCRP在大鼠肝脏中的蛋白表达显著降低了25.9％、38．6％、37．0％、54．1％、53．1％、66．8％；BCRP在大鼠肝脏中的mRNA表达显著降低了14．8％、34．8％、44．3％、40．9％、51．3％、43．5％。结论高原低氧环境下，肝脏中MDR1、MRP1、BCRP蛋白及mRNA表达均减少。此发现为高原地区合理设计临床用药方案提供理论依据。

英文摘要：

Objective The present study was designed to investigate the regulation of Drug Transports by acute and chronic hypoxia in high altitude environments.Methods The rats were randomly divided into control group ,plain group, acute middle altitude hypoxia group, chronic middle altitude hypoxia group, acute high altitude hypoxia group,chronic high altitude hypoxia group, chronic middle altitude hypoxia group returned to Xining and chronic high altitude hypoxia group returned to Xining.ELISA and real-time quantitative PCR were used to analyze the pro tein and mRNA expression of MDR1, MRP1 and BCRP, respectively.Results Compared with the control group,The protein expression of MDR1 was significantly decreased by 16,3%, 27.3%, 27.3%, 33.1%, 39.0%, 41.3% in the rest of the groups,respectively,and the mRNA expression of MDR1 was significantly decreased by 33.0%,34.0%, 48.1% ,47.2%,48.1%, 52.8%, respectively.The protein expression of MRP 1 was significantly decreased by 19.4%, 31.7%, 34.0%, 50.9%, 52.0%, 56.0%, respectively, and the mRNA expression of MRP 1 was significantly decreased by 18.9%, 23.4%, 36.9%, 30.6%, 27.0R, 29.7% ,respectively. The protein expression of BCRP was significantly decreased by 25.9%, 38.6%, 37.0%, 54.1%, 53.1%, 66.8%, respectively, and the mRNA expression of BCRP was significantly decreased by 14.8%, 34.8%, 44.3%, 40.9%, 51.3%, 43.5%, respectively. Conclusion The present study demonstrates that the protein and mRNA expression of MDR1 ,MRP1 and BCRP are significantly less in rats exposed to AMH,AHH,CHH, CMH, R-CMH and R-CHH.This study may play an important role in the rational design of clinical drugs at a high altitude.