中国临床药理学与治疗学
中國臨床藥理學與治療學
중국림상약이학여치료학
CHINESE JOURNAL OF CLINICAL PHARMACOLOGY
2006年
1期
45-50
,共6页
吴玉林%马秉亮%祝浩杰%刘国卿
吳玉林%馬秉亮%祝浩傑%劉國卿
오옥림%마병량%축호걸%류국경
P-糖蛋白%洛美利嗪%罗丹明123%大鼠脑微血管内皮细胞%流式细胞术%Transwell
P-糖蛋白%洛美利嗪%囉丹明123%大鼠腦微血管內皮細胞%流式細胞術%Transwell
P-당단백%락미리진%라단명123%대서뇌미혈관내피세포%류식세포술%Transwell
P-glycoprotein%Lomerizine%rat brain microvessel endothelialcells%flow cytometry%transwell%rhodamine123
目的:研究洛美利嗪对原代培养的大鼠脑微血管内皮细胞(RBMECs)上P-糖蛋白(P-gp)功能和表达的影响.方法:使用流式细胞术分析洛美利嗪对P-gp底物-罗丹明123(rhodamine123, Rh123)在RBMECs中外排的影响,使用流式细胞术分析了洛美利嗪对RBMECs上P-gp表达的影响,应用RT-PCR技术分析了洛美利嗪对RBMECs mdr1基因mRNA水平表达的影响, 还使用Transwell模型研究了洛美利嗪对Rh123通透RBMECs单层细胞转运的影响.结果:洛美利嗪通过抑制了RBMECs胞内Rh123的外排;洛美利嗪对P-gp功能的影响与RBMECs上P-gp及mdr1基因mRNA表达无关;在Transwell模型中,洛美利嗪还能显著增加Rh123跨RBMECs单层细胞膜的、经上室至下室的转运,并抑制相反方向的Rh123的转运.结论:洛美利嗪能显著地抑制RBMECs上P-gp的活性,并对P-gp底物的跨细胞转运产生影响.
目的:研究洛美利嗪對原代培養的大鼠腦微血管內皮細胞(RBMECs)上P-糖蛋白(P-gp)功能和錶達的影響.方法:使用流式細胞術分析洛美利嗪對P-gp底物-囉丹明123(rhodamine123, Rh123)在RBMECs中外排的影響,使用流式細胞術分析瞭洛美利嗪對RBMECs上P-gp錶達的影響,應用RT-PCR技術分析瞭洛美利嗪對RBMECs mdr1基因mRNA水平錶達的影響, 還使用Transwell模型研究瞭洛美利嗪對Rh123通透RBMECs單層細胞轉運的影響.結果:洛美利嗪通過抑製瞭RBMECs胞內Rh123的外排;洛美利嗪對P-gp功能的影響與RBMECs上P-gp及mdr1基因mRNA錶達無關;在Transwell模型中,洛美利嗪還能顯著增加Rh123跨RBMECs單層細胞膜的、經上室至下室的轉運,併抑製相反方嚮的Rh123的轉運.結論:洛美利嗪能顯著地抑製RBMECs上P-gp的活性,併對P-gp底物的跨細胞轉運產生影響.
목적:연구락미리진대원대배양적대서뇌미혈관내피세포(RBMECs)상P-당단백(P-gp)공능화표체적영향.방법:사용류식세포술분석락미리진대P-gp저물-라단명123(rhodamine123, Rh123)재RBMECs중외배적영향,사용류식세포술분석료락미리진대RBMECs상P-gp표체적영향,응용RT-PCR기술분석료락미리진대RBMECs mdr1기인mRNA수평표체적영향, 환사용Transwell모형연구료락미리진대Rh123통투RBMECs단층세포전운적영향.결과:락미리진통과억제료RBMECs포내Rh123적외배;락미리진대P-gp공능적영향여RBMECs상P-gp급mdr1기인mRNA표체무관;재Transwell모형중,락미리진환능현저증가Rh123과RBMECs단층세포막적、경상실지하실적전운,병억제상반방향적Rh123적전운.결론:락미리진능현저지억제RBMECs상P-gp적활성,병대P-gp저물적과세포전운산생영향.
AIM: To study the effect of Lomerizine on the activity of P-glycorprotein (P-gp) in primary cultured rat brain microvessel endothelial cells (RBMECs). METHODS: Flow cytometry was used to study the efflux of rhodamine123 (Rh123) and expression of P-gp in RBMECs. RT-PCR was used to measure the expression in mRNA level of mdr1 gene in RBMECs. Transwell model was used to detect the influence of Lomerizine on the transport of Rh123 through RBMECs monolayer. RESULTS: Lomerizine inhibited the efflux of Rh123 in RBMECs. No changes of P-gp and mdr1 gene mRNA expression were detected in RBMECs after the treatment with 30 μmol·L-1 Lomerizine for 72 h. In the study of Transwell model, Lomerizine increased significantly the transport of Rh123 through RBMECs monolayer from upper compartments to lower compartments, and inhibited obviously the transport in reverse direction. CONCLUTION: The effect of Lomerizine on the activity of P-gp was mainly via its direct inhibitory effect on the function of P-gp in RBMECs and the transport of P-gp substrates in BBB may be affected by lomerizine.
