期刊文献+

海马硬化致耐药性颞叶内侧癫痫的耐药基因蛋白表达及意义 被引量:2

Expressions of drug-resistance related genes and the significance in sclerotic hippocampi from patients with drug-resistant mesial temporal lobe epilepsy
原文传递
导出
摘要 目的观察耐药性颞叶内侧癫痫硬化海马中有关耐药基因蛋白的表达并探讨其临床意义。方法对经手术治疗取自16例颞叶内侧癫痫的硬化海马标本进行免疫组化染色观察p-糖蛋白170(p-gp170)、谷胱甘肽硫转移酶-π(GST-π)、拓扑酶II(TOPII)、胸苷合成酶(TS)及O-6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)的表达。结果p-gp170和GST-π在硬化海马组织中神经细胞、血管内皮细胞及胶质细胞均有表达,而以血管内皮细胞和胶质细胞阳性表达尤为突出。TOPII、TS和MGMG在硬化海马中无明显阳性表达。结论长期应用抗癫痫药物可能诱导p-gp170和GST-π表达增强,促进抗癫痫药物的排出与代谢,引起耐药。TOPII、TS和MGMG可能与癫痫耐药机制无关。 Objective To observe the expressions of drug--resistance related genes in sclerotic hippocampi from patients with drug--resistant mesial temporal lobe epilepsy in order to insight into mechanisms with drug--resistance in epilepsy. Methods The expressions of glycoprorein p 170( p--gp170), glutathione-- S-- transferase π (GST-- π), topoisomerase II (TOP II ), Thymidylate Synthase(TS), and O6--methylguanine DNA methyltransferase (MGMT)in the sclerotic hippocampi operatively taken from 16 patients with refractory mesial temporal lobe epilepsy were detected using immunohistochemieal staining. Results Apparent expressions of p-- gp170 and GST--π were observed in neurons, vascular endothelial cells and glial cells in the sclerotic hippocampi, especially more remarkable in vascular endothelial cells and glial cells. TOPII, TH and MGMG were not expressed apparently in the sclerotic hippocampi. Conclusion Long-- term usage of antiepileptic drugs could promote the expressions of p--gp170 and GST--π ,which in turn enhance the excretion and metabolism of the drugs used, leading to the phenomenon of drug--resistance. TOPII.TS and MGMG could possibly be unrelated with the drug--resistance phenomenon in chronic epilepsy.
出处 《立体定向和功能性神经外科杂志》 2009年第1期6-9,共4页 Chinese Journal of Stereotactic and Functional Neurosurgery
关键词 颞叶内侧癫痫 海马硬化 P-糖蛋白170 谷胱甘肽硫转移酶-π Mesial temporal lobe epilepsy Hippocampal sclerosis Glycoprotein p 1701 Glutathione-- S-- transferase π
  • 相关文献

参考文献9

  • 1Soranzo N, Cavalleri GL, Weale ME, et al. Identifying candidate causal variants responsible for altered activity of the ABCB1 multidrug resistance gene [ J]. Genome Res, 2004,14(7) : 1333- 1344.
  • 2Lazarowski A, Ramos AJ, Garcia--Rivello H, et al. Neuronal and glial expression of the multidrug resistance gene product in an experimental epilepsy model[J]. Cellular and Molecular Neurobiology, 2004,24 (1) : 77- 85.
  • 3Lazarowski A, Lubieniecki F, Camarero S, et al. Multi drug resistance proteins in tuberous sclerosis and refractory epilepsy[J]. Pediatr Neurol, 2004,30 : 102- 106.
  • 4Lazarowski A, Sevlever G, Taratuto A, et al Tuberous scle rosis associated with MDR1 gene expression and drug-resist ant epilepsy[J]. Ped Neurol, 1999,21:731-734.
  • 5Aronica E, Gorter J A, Jansen GH, et al. Expression and celluar distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: focal cortical dysplasia and glioneuronal tumors[J]. Neuro science, 2003,118 : 417-429.
  • 6Siddiqui A, Kerb R, Weale M, et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug--transporter gene ABCBI[J]. N Engl Med, 2003,348 : 1442- 1448.
  • 7Potschka H, Fedrowitz M, Loscher W. P--glycoprotein and multidrug resistance--associated protein are involved in the regulation of extracellular level of the major antiepileptic drug carbamazepine in the brain[J]. Neuroreport, 2001,12 : 3557-3560.
  • 8彭佑群,王景周,王学峰.托吡酯对大鼠星形细胞内谷胱甘肽硫转移酶及多药耐受基因的影响[J].中国新药与临床杂志,2004,23(5):279-282. 被引量:10
  • 9龚玉来,王学峰,龚云,汪建华,朱曦,晏勇,栾国明,王玉平,张国君,李永林,张建国.谷胱苷肽硫转移酶在耐药性癫痫脑组织中的表达[J].中华神经外科杂志,2006,22(8):510-512. 被引量:4

二级参考文献16

  • 1Park SK, Kang D, Noh Dong-Young, et al. Reproductive factors,glutathione S-thansferase M1 and T1 genetic polymorphism and breast cancer risk. Breast Cancer Research & Treatment, 2003, 78: 89-96.
  • 2Huang Jingxiang, Tan Puay-Hoon, Thiyagarajan, et al. Prognostic significance of glutathione S-transferase-pi in invasive breast cancer.Modem Pathology, 2003, 16: 558-565.
  • 3Kantor RR, Giardina SL, Bartolazzi A, et al. Monoclonal antibodies to glutathione S-transferase-[ pi ] immunohistochemical analysis of human tumors and cancers. Int J Cancer, 1991,47 : 193-201.
  • 4Michael RP, James W, Keelan J. Drug transfer and metabolism by the human placenta. Clinical Pharmacokinetics, 2004, 43: 487-514.
  • 5Potschka H, Fedrowitz M, Loseher W. P-glyeoprotein and muhidrug resistance-associated protein are involved in the regulation of extracellular levels of the major antiepileptic drug carbamazepine in the brain. Neurereport, 2001, 12 : 3557-3560.
  • 6Nemeth H, Robotka H, Kis Z, et al. Kynurenine administered together with prebenecid markedly inhibits pentylenetetrazol-induced seizures. An electrephysiological and behavioural study.Neuropharmacology, 2004, 47: 916-925.
  • 7Scism JL, Powers KM, Artru AA, et al. Probenecid-inhibitable efflux transport of valproic acid in the brain parenchymal cells of rabbits: a microdialysis study. Brain Res, 2000, 24, 884: 77-86.
  • 8Yang MS, Wang XF, Qin Wei, et al. Evidence for a major susceptibility locus at 11q22. 1-23.3 has been detected in a large Chinese family with pure grand mal epilepsy. Neuroscience Letters,2003, 346: 133-136.
  • 9张鑫,谭启富,王卫萍,李芳秋,陈亚利,武建国.药物难治性癫痫患者脑内多种耐药基因表达的初步研究[J].中华神经外科杂志,1999,15(6):336-338. 被引量:6
  • 10吴逊,沈鼎烈.难治性癫痫[J].中华神经科杂志,1998,31(1):4-4. 被引量:133

共引文献12

同被引文献13

引证文献2

二级引证文献7

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部