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�й�ҩѧ��־ 2011, Vol. 46 Issue (1) :48-53    DOI:
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��ƽ�ɣ���ά�������*������ƽ
���ϴ�ѧ���Ŷ�ҽԺ�ٴ�ҩѧ�о��ң���ɳ 410011
FANG Ping-fei�� GAO Wei�� LI Huan-de*�� LIU Yi-ping
Clinical Pharmaceutical Research Institute�� Xiangya Second Hospital�� Central South University�� Changsha 410011�� China

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Abstract�� OBJECTIVE To study the effects of four anti-tuberculosis drugs on the function and expression of P-glycoprotein and the MDR1 mRNA expression�� for explaining the rationality of different combination in anti-tuberculosis chemotherapy. METHODS The effect of the drugs on P-glycoprotein function was analyzed using Rh-123 assay. The flow cytometry was used to determine the intracellular Rh-123 concentration and the expression of P-glycoprotein in Caco-2 cells. Real-time fluorescent quantitative polymerase chain reaction was used to measure the expression of MDR1 gene mRNA in Caco-2 cells. RESULTS After the intervention for 20 d�� the therapeutic doses of isoniazid and ethambutol decreased the accumulation of rhodamine123 in Caco-2 cells significantly compared with that of negative control group (P<0.05. The therapeutic doses of isoniazid and ethambutol both up-regulated the cellular P-glycoprotein protein and MDR1 mRNA expression levels (P<0.05. Compared with the controls�� the total quantity of P-glycoprotein were 3.5 and 3.8 folds higher than that of controls�� and the total levels of MDR1 mRNA expression were 11.5 and 11 folds higher than that of controls�� respectively. Therapeutic doses of levofloxacin increased the accumulation of rhodamine123 in Caco-2 cells significantly higher than that of negative control group (P<0.05. The therapeutic doses of levofloxacin down-regulated the cellular P-glycoprotein protein and MDR1 mRNA expression levels (P<0.05. Compared with the controls�� the total levels of P-glycoprotein and MDR1 mRNA expression were 50% and 32% of controls�� respectively. Pyrazinamide showed no significant interaction with P-glycoprotein. CONCLUSION Therapeutic doses of isoniazid and ethambutol might be inducer of P-glycoprotein�� levofloxacin might be inhibitors of p-glycoprotein�� and pyrazinamide showed no significant interaction with P-glycoprotein.
Keywords�� anti-tuberculosis drugs,   P-glycoprotein,   Caco-2 cells,   MDR1,   isoniazid,   levofloxacin,   ethambutol,   pyrazinamide     
�ո�����: 2011-11-11;
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.���Ƽ�����4�ֿ����ҩ����Caco-2ϸ����P-gp�໥�����о�[J]  �й�ҩѧ��־, 2011,V46(1): 48-53
.Initial Study on Interaction between Therapeutic Doses of Four Anti-Tuberculosis Drugs and P-Glycoprotein in Caco-2 Cells[J]  Chinese Pharmaceutical Journal, 2011,V46(1): 48-53
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