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研究癫痫耐药机制及克服的办法已成为重要的课题,近年来研究发现多耐药基因(multidrug resistance,MDR1,ABCB1)及其表达产物P-gp蛋白在动物模型及人类难治性癫痫脑组织中表达明显增多,P-gp蛋白与耐药机制的形成有关,应用P-gp蛋白抑制剂能够增加细胞内抗癫痫药物(antiepileptic drugs,AEDs)浓度,减少其应用。国外大多数研究发现MDR1基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)影响MDR1功能和P-gp蛋白表达,与难治性癫痫的耐药性相关,但是有的学者持相反观点,可能与研究的单倍体局限性有关。标签单核苷酸多态性SNP(tag SNPs)能够特异识别某一单倍型,将来通过对MDR1基因tag SNPs研究,对难治性癫痫的的遗传学研究、发现其遗传标志、早期诊断、个体化治疗有重要的意义。
In recent years, it has been found that multidrug resistance (MDR1, ABCB1) and its expression product P-gp protein play an important role in animal models and in human refractory epilepsy brain tissue The expression of P-gp protein was related to the formation of drug resistance mechanism. The application of P-gp inhibitor could increase the concentration of intracellular antiepileptic drugs (AEDs) and decrease its application. Most foreign studies found that MDR1 gene single nucleotide polymorphisms (single nucleotide polymorphisms, SNPs) affect the function of MDR1 and P-gp protein expression, and resistance to refractory epilepsy, but some scholars hold the opposite view, May be related to the study of haploid limitations. Tag SNPs can specifically identify haplotypes. In the future, through the study of tag SNPs of MDR1 gene and the genetic study of refractory epilepsy, it is found that the genetic markers, early diagnosis, Individualized treatment has important implications.