X射线照射对大鼠CYP1A2和CYP2E1活性及表达水平的调控
Regulation of X-Ray Irradiation on the Activity and Expression Levels of CYP1A2 and CYP2E1 in Rats.
作者信息
Li Xiang-Yang, Qu Ning, Wang Xue-Jun, Yang Jian-Xin, Xin Yuan-Yao, Zhu Jun-Bo, Bai Xue, Duan Ya-Bin
机构信息
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China.
Medical College, Qinghai University, Xining, China.
出版信息
Front Pharmacol. 2020 Jan 28;10:1575. doi: 10.3389/fphar.2019.01575. eCollection 2019.
The objective of this study was to investigate the regulation of X-ray irradiation and its effect on the activity and protein and mRNA expression levels of CYP1A2 and CYP2E1 in rats. Rats were randomly divided into 0 Gy (control), 1 Gy (low-dose irradiation), and 5 Gy (high-dose irradiation) groups. CYP1A2 and CYP2E1 activity was evaluated from changes in pharmacokinetic parameters of caffeine and chlorzoxazone, respectively. The plasma concentrations of the probe drugs were determined by high-performance liquid chromatography (HPLC). Enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) tests were used to analyze the protein and mRNA expression levels of CYP1A2 and CYP2E1, respectively. The AUC of caffeine was decreased by 1.7- and 2.5-fold, and the CL was increased by 1.8- and 2.6-fold in the 1 Gy and 5 Gy groups, respectively, compared to the 0 Gy group. The AUC of chlorzoxazone was 1.4- and 1.8-fold lower, and the CL was 1.4- and 1.9-fold higher in the 1 Gy and 5 Gy groups, respectively, compared to the 0 Gy group. The metabolism of caffeine and chlorzoxazone increased under X-ray irradiation as CL levels increased and AUC levels decreased, suggesting that CYP1A2 and CYP2E1 activity is enhanced in rats after X-ray irradiation. Compared to that of the 0 Gy group, the protein expression level of CYP1A2 was measured as 28.3% and 38.9% higher in the 1 Gy and 5 Gy groups, respectively. The protein expression level of CYP2E1 was 48.4% higher in the 5 Gy group compared to the 0 Gy group, and there was no statistically significant difference between 0 Gy and 1 Gy. Compared to the 0 Gy group, the mRNA expression level of CYP1A2 was 200% and 856.3% higher in the 1 Gy and 5 Gy group, respectively, whereas the mRNA expression level of CYP2E1 was 89.0% and 192.3% higher in the 1 Gy and 5 Gy groups, respectively. This study reveals significant changes in the activity and protein and mRNA expression levels of CYP1A2 and CYP2E1 in rats after exposure to X-ray irradiation.
本研究的目的是探讨X射线照射的调控及其对大鼠CYP1A2和CYP2E1活性、蛋白质和mRNA表达水平的影响。将大鼠随机分为0 Gy（对照组）、1 Gy（低剂量照射组）和5 Gy（高剂量照射组）。分别通过咖啡因和氯唑沙宗药代动力学参数的变化来评估CYP1A2和CYP2E1的活性。采用高效液相色谱法（HPLC）测定探针药物的血浆浓度。分别用酶联免疫吸附测定法（ELISA）和实时聚合酶链反应（PCR）检测来分析CYP1A2和CYP2E1的蛋白质和mRNA表达水平。与0 Gy组相比，1 Gy组和5 Gy组咖啡因的AUC分别降低了1.7倍和2.5倍，CL分别升高了1.8倍和2.6倍。与0 Gy组相比，1 Gy组和5 Gy组氯唑沙宗的AUC分别降低了1.4倍和1.8倍，CL分别升高了1.4倍和1.9倍。随着CL水平升高和AUC水平降低，X射线照射下咖啡因和氯唑沙宗的代谢增加，这表明X射线照射后大鼠体内CYP1A2和CYP2E1的活性增强。与0 Gy组相比，1 Gy组和5 Gy组CYP1A2的蛋白质表达水平分别高出28.3%和38.9%。与0 Gy组相比，5 Gy组CYP2E1的蛋白质表达水平高出48.4%，0 Gy组和1 Gy组之间无统计学显著差异。与0 Gy组相比，1 Gy组和5 Gy组CYP1A2的mRNA表达水平分别高出200%和856.3%，而1 Gy组和5 Gy组CYP2E1的mRNA表达水平分别高出89.0%和192.3%。本研究揭示了大鼠在接受X射线照射后CYP1A2和CYP2E1的活性、蛋白质和mRNA表达水平发生了显著变化。
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