The Activity, Protein, and mRNA Expression of CYP2E1 and CYP3A1 in Rats after Exposure to Acute and Chronic High Altitude Hypoxia
The Activity, Protein, and mRNA Expression of CYP2E1 and CYP3A1 in Rats after Exposure to Acute and Chronic High Altitude Hypoxia
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DOI：
10.1089/ham.2014.1026
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发表时间：
2014-12-01
影响因子：
2.1
通讯作者：
Duan, Yabin
中科院分区：
文献类型：
--
作者：
Li, Xiangyang;Wang, Xuejun;Duan, Yabin
Xiangyang，Li，Xuejun Wang，Yongping Li，Junbo Zhu，Xiaodong Su，Xingchen Yao，Xueru Fan，and Yabin Duan.急、慢性高原缺氧大鼠细胞色素P450 2 E1和3A 1活性、蛋白和mRNA表达的变化High Alt Med Biol 15：491-496，2014.在大鼠中检查暴露于急性和慢性高原缺氧对CYP 2 E1和CYP 3A 1的活性和表达的影响。将大鼠分为低海拔（LA，400 m）、急性中度高原缺氧（AMH，2800 m）、慢性中度高原缺氧（CMH，2800 m）、急性高原缺氧（AHH，4300 m）和慢性高原缺氧（CHH，4300 m）组。所有五组均口服探针药物。采用反相高效液相色谱法测定血清中探针药物及其代谢产物的浓度。分别使用代谢产物与氯唑沙宗和睾酮的比值评价CYP 2 E1和CYP 3A 1的活性。ELISA法检测肝微粒体中CYP 2 E1和CYP 3A 1的蛋白表达，实时荧光定量PCR法检测肝微粒体中CYP 3A 1的mRNA表达。慢性高原低氧可引起大鼠体内CYP 2 E1和CYP 3A 1活性、蛋白和mRNA表达的显著下降。急性高原缺氧对大鼠CYP 2 E1和CYP 3A 1的活性、蛋白质和mRNA表达无明显影响。慢性高原低氧暴露后，大鼠肝细胞色素P450酶2 E1和3A 1的活性、蛋白和mRNA表达均发生明显变化。
Xiangyang, Li, Xuejun Wang, Yongping Li, Junbo Zhu, Xiaodong Su, Xingchen Yao, Xueru Fan, and Yabin Duan. The activity, protein, and mRNA expression of CYP2E1 and CYP3A1 in rats after exposure to acute and chronic high altitude hypoxia. High Alt Med Biol 15:491-496, 2014.The effects of exposure to acute and chronic high altitude hypoxia on the activity and expression of CYP2E1 and CYP3A1 were examined in rats. Rats were divided into low altitude (LA, 400m), acute moderate altitude hypoxia (AMH, 2800m), chronic moderate altitude hypoxia (CMH, 2800m), acute high altitude hypoxia (AHH, 4300m), and chronic high altitude hypoxia groups (CHH, 4300m). Probe drugs were administrated orally to all five groups. Then the serum concentration of probe drug and its metabolite was determined by RP-HPLC. The activity of CYP2E1 and CYP3A1 was evaluated using the ratio of the metabolite to chlorzoxazone and testosterone, respectively. ELISA and real-time PCR were used to analyze the protein and mRNA expression of CYP2E1 and CYP3A1 in liver microsomes, respectively. Chronic high altitude hypoxia caused significant decreases in the activity and protein and mRNA expression of rat CYP2E1 and CYP3A1 in vivo. Acute high altitude hypoxia was not found to change the activity, protein or mRNA expression of rat CYP2E1 or CYP3A1. This study showed significant changes in the activity and protein and mRNA expression of CYP2E1 or CYP3A1 in rats after exposure to chronic high altitude hypoxia.