目的 利用抗氧化反应元件（ARE）调控荧光素酶（Luc）报告基因的表达水平，建立抗氧化药物筛选细胞模型。方法 构建由ARE调控Luc表达的重组质粒载体pARE-Luc-Neo，使用FuGENE^? HD转染剂将重组质粒转染人胚肾上皮Hek293细胞，通过G418进行筛选，使用稀释法挑选阳性单克隆细胞，经抗氧化蛋白诱导剂TBHQ诱导，检测细胞中Luc的活性，筛选Luc高活性的单克隆细胞株。利用白藜芦醇和姜黄素评价阳性克隆的筛选效果，观察5个中药单体穿心莲内酯、隐丹参酮、水飞蓟素、苦参碱和虎杖苷在不同浓度（0、3.125、6.25、12.5、25、50、100 μmol/L）时对Luc表达水平的影响。结果 通过检测Luc活性，筛选获得Hek293-ARE，该细胞中的Luc的表达水平受ARE调控，且在一定范围内与诱导剂的浓度呈相关性。穿心莲内酯、隐丹参酮与水飞蓟素有较好的诱导效果。结论 建立的抗氧化药物细胞筛选模型可有效地、高通量地用于抗氧化药物的初步筛选。

Objective To compare the pharmacokinetics in rats and tissue distribution in mice of tanshinone II_A (TNS) lipid microsphere and sodium tanshinone II_A silate (STS) injection after iv injection. Methods A sensitive and specific RP-HPLC method was established to determine the concentration of TSN and STS in rat plasma and mice tissue. The TSN and STS levels in plasma of rats and tissues of mice were compared after iv single dose administration of TSN lipid microsphere (5.40 mg/kg) and STS injection (7.27 mg/kg), and the results were fitted by pharmacokinetic and statistic analyses. Results The bioavailability (AUC_0-∞) and peak concentration (C_max) values of TSN were 2.14 and 2.22 folds as those of STS, the clearance (CL), apparent volume of distribution (V), and mean repair time (MRT) values of TSN were lower (P < 0.01), and other pharmacokinetic parameters had no significant deviation. The results on the tissue distribution of TSN and STS in mice showed that the contents of TSN in heart, liver, spleen, lung, and kidney tissues were 1.94, 0.11, 0.98, 1.65, and 0.28 folds as those of STS with the same molar dose, and the content of TSN in brain tissue increased more significantly than that of STS which has not been detected. Conclusion The pharmacokinetics and tissue distribution of TSN and STS at the same molar dose have significant differences, the AUC and C_max values of TSN are higher, and the concentration of TSN could be increased in heart, brain, and lung tissues significantly, compared with those of STS.

江西省科技支撑计划（2010BSB02602）