难治性癫痫相关耐药蛋白在局灶性皮质发育不良脑组织中的表达

Expression of refractory epilepsy related drug resistance proteins in brain tissue of focal cortical dysplasia

目的 通过对P-糖蛋白、多药耐药相关蛋白和肺耐药相关蛋白在难治性癫痫相关局灶性皮质发育不良脑组织中表达部位的初步研究,以及对其在不同程度病变脑组织中表达量的比较,进一步阐明难治性癫疴的耐药机制,为癫痫患者的临床合理用药提供理论依据.方法 选取16例难治性癫痫患者手术切除脑组织标本作为患者组（局灶性皮质发育不良Ⅰ型和Ⅱ型患者各8例）,5例无癫痫发作病史的胶质瘤患者手术切除脑组织标本的非病灶区域作为对照组.应用Envision二步法进行免疫组织化学标记,观察3种耐药蛋白在脑组织中的表达部位和表达强度;应用Western blot法进行SDS-聚丙烯酰胺凝胶电泳,对3种耐药蛋白在脑组织中的表达进行定量分析.结果 P-糖蛋白主要表达于毛细血管内皮细胞,多药耐药相关蛋白主要表达于脑组织内的神经元成分,肺耐药相关蛋白的表达则涌盖了毛细血管内皮细胞、气球细胞及病灶区域部分基质.3种耐药蛋白在局灶性皮质发育不良脑组织中的表达均显著高于对照组脑组织（P-糖蛋白：0.520±0.121,多药耐药蛋白：0.132±0.018,肺耐药相关蛋白：0.092 4-0.018,U=0.000,P〈0.01）,其中P-糖蛋白和肺耐药相关蛋白在局灶性皮质发育不良Ⅱ型患者的病灶区域（3.809±0.842、0.655±0.303）表达高于病灶周围区域（2.636 4±0.622、0.290±0.096,U=6.000、4.500,P〈0.01）.结论 P-糖蛋白、多药耐药相关蛋白和肺耐药相关蛋白在不同程度的局灶性皮质发育不良脑组织中具有不同的表达部位和表达量,提示其作用机制和作用强度有所差异.

Objective To study the locations of P-glycoprotein（P-gp）,multi-drug resistanceassociated protein （MRP） and lung resistance.related protein（LRP）in brain tissue of focal cortical dysplasia （FCD） and to compare the quantity of these proteins in different brain tissues in an effort to study the mechanism of refractory epilepsy and to provide theoretical basis for medical treatment in patients with epilepsy.Methods The brain tissues of 16 cases with refractory epilepsy were collected during surgery,including 8 cases of focal cortical dysplasia type Ⅰ（FCD Ⅰ）and 8 cases of focal cortical dysplasia type Ⅱ （FCD Ⅱ） Five cases of glioma without history of epilepsy were included as the control group.Envision method was used to observe the location and intensity of expression of these three proteins.Western-Blot was used to analyze these proteins quantitatively.Results In brain tissue,the locations of P-glycoprotein,multi-drug resistance-associated protein and lung resistance-related protein were difierent.P-gp located mainly in capillary endothelial cells;MRP in neurons components;the location of LRP included capillary endothelial cells,balloon cells and the matrix of lesions.The expressions of three proteins in brain tissue of FCD were significantly higher than in control group（P-gp：0.520 ±0.121,MRP：0.132±0.018,LRP：0.092.±0.018,U=0.000,P〈0.01）.The expressions of P-gp and LRP in lesions of FCD Ⅱ（3.809 ±0.842 and 0.655±0.303,respectively）were higher than that in surrounding regions（2.636 ±0.622 and 0.290±0.096,U value were 6.000 and 4.500,both P〈0.01）.Conclusions P-gp,MRP and LRP expressed at different position of focal cortical dysplasia,suggesting that their roles were distinctive.