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抗癫癎药物诱导对血脑屏障上P-糖蛋白功能与表达的影响 被引量:2

Antiepileptic drugs up-regulated activity and expression of P-glycoprotein in blood-brain barrier of rats
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摘要 目的研究长期使用抗癫疒间药物(AEDs)对大鼠脑中P-糖蛋白(P-gp)功能活性和表达水平的影响。方法选择苯巴比妥、苯妥英钠和卡马西平三个典型AEDs,在大鼠体内连续给药21天,然后观察脑组织中皮质和海马P-gp的改变。结果底物罗丹明123转运实验表明P-gp功能增强,进一步通过Western Blot分析表明P-gp表达增强,并用免疫组化染色显示其细胞定位在血脑屏障上。结论长期AEDs诱导可以同时导致大鼠血脑屏障上P-gp功能活性和表达水平的升高。 Objective To investigate whether chronic exposure of antiepileptic drugs(AEDs) increased P-glycoprotein(P-gp) function and expression in brain of rats.Methods Three drugs phenobarbital(PB),phenytion(PHT) and carbamazepine(CBZ) were orally given to rats for successive 21 days,P-gp activity and levels in brain was assessed.Results Tissue-to-plasma concentration ratios of Rho123 were significantly decreased in cerebral cortex and hippocampus.Immunohistochemistry result showed that up-regulation of the P-gp mainly occurred in capillary endothelial vessels.Western blot result suggested that the protein level of P-gp in cortex and hippocampus of rats exposed to drugs was significantly higher than that of control rats.Conclusion Chronic exposure of AEDs may increase P-gp function and level in brain of rats.
出处 《徐州医学院学报》 CAS 2010年第4期230-233,共4页 Acta Academiae Medicinae Xuzhou
关键词 P-糖蛋白 血脑屏障 抗癫间疒药物 诱导 P-glycoprotein Blood-brain barrier Antiepileptic drugs Induction
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  • 1Toth K, Vaughan MM, Slocum HK,et al. New immunohistochemi-cal "sandwich" staining method for mdr1 P-glycorprotein detection with JSB-1 monoclonal antibody in formalin-fixed, paraffin-embedded human tissues [J]. Am J Pathol,1994,144:227-236.
  • 2Cordon-Cardo C, O'Brien JP, Casals D, et al. Multidrug-resistence gene(P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites [J]. Proc Natl Acad Sci USA, 1989,86:695-598.
  • 3Kanazawa T, Morita T, Harada K, et al. Selective effect of KB-2796, a new calcium entry blocker, on cerebral circulation: A comparative study of the effects of calcium entry blockers on cerebral and peripheral arterial blood flows [J]. J Cardiovasc Pharmacol,1990,16:430-437.
  • 4Shiraki N, Hamada A, Ohmura T, et al. Increase in doxorubicin cytotoxicity by inhibition of P-glycoprotein activity with lomerizine[J]. Biol Pharm Bull, 2001, 24:555-557.
  • 5Abbott NJ, Hughes CCW, Revest PA, et al. Development and characterization of a rat brain capillary endothelial culture: towards an in vitro blood-brain barrier[J]. J Cell Sci, 1992,103:23-37.
  • 6Petriz J, Garcia-Lopez J. Flow cytometric analysis of P-glycoprotein function using Rhodamine 123 [J]. Leukemia,1997,11:1124-1130.
  • 7Levin V. Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability [J]. J Med Chem,1980,23:682-684.
  • 8Schinkel AH, Smit JJM, Tellingen O van,et al. Disruption of the mouse mdr1a P-Glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs [J]. Cell,1994,77:491-502.
  • 9LooTW,ClarkeDM.Superfoldingofthepartiallyunfoldedcore glycosylatedintermediateofhumanP glycoproteinintothematureenzymeispromotedbysubstrate inducedtransmembranedomaininteractions[].Journal of Biochemistry.1998
  • 10Marie JP,Zittou nR,Siki cB.Multidrugresistance(mdr1)geneexpressioninadultacultleukemiias:correlationswithtreatmentoutcomeandinvitrodrugsensitivity[].Blood.1991

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  • 1肖争,王学峰,晏勇,栾国明,阎丽.难治性癫癇患者脑组织中5种耐药基因产物的同步表达及临床意义[J].中华神经科杂志,2004,37(6):500-503. 被引量:17
  • 2Racine RJ. Modification of seizure activity by electrical stimulation : Cortical areas [ J ]. Electroencephalogr Clin Neurophysiol, 1975,38 ( 1 ) : 1 - 12.
  • 3Liu B ,Wang T,Wang L,et al. Up - regulation of major vault protein in the frontal cortex of patients with intractable frontal lobe epilepsy [ J 1. J Neurol Sci,2011,308( 1 -2) :88 -93.
  • 4Aronica E, Gorter JA, van Vliet EA, et al. Overexpression of the human major vault protein in gangliogliomas [ J ]. Epilepsia, 2003,44 ( 9 ): 1166 - 1175.
  • 5Guo Z,Zhu J, Zhao L, et al. Expression and clinical significance of multidrug resistance proteins in brain tumors [ J ]. J Exp Clin Cancer Res , 2010,29 : 122.
  • 6Sisodiya SM, Martinian L, Scheffert GL, et al. Vascular colocalization of P - glycoprotein, multidrug - resistance associated proteinl, breast eance resistance protein and major vault protein in human epileptogenic pathologies. Neuropathology and applied [ J ]. Neurobiology, 2009,32 (1) :51 -63.
  • 7Van Vliet EA, Aronica E, Redeker S, et al. Expression and cellular distribution of major vault protein : A putative marker for pharmacoresis- tance in a rat model for temporal lobe epilepsy[J]. Epilepsia ,2004,45 (12) :1506 -1516.
  • 8Luna - Tortos C, Fedrowitz M, Loscher W. Evaluation of transport of common antiepileptic drugs by human multidrug resistance - associated proteins ( MRP1,2 and 5 ) that are overexpressed in pharmacoresistant epilepsy[ J]. Neuropharmacology,2010,58 (7) : 1019 - 1032.
  • 9Labbozzetta M, Notarbartolo M, Poma P, et al. Curcumin as a possible lead compound against hormone - independent, muhidrug - resistant breast cancer[J] .Ann N Y Acad Sci,2009,1155:278 -283.
  • 10Sinha S, Siddiqui KA. Definition of intractable epilepsy[J]. Neurosciences ( Riyadh), 2011, 16 : 3 - 9.

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