婴儿痉挛外周血多药耐药基因1及P-糖蛋白表达研究

Research on multiple drug resistance gene and expression of P-glycoprotein in peripheral blood in patients with infantile spasms

目的检测婴儿痉挛(IS)外周血多药耐药基因1(MDR1)及其产物P-糖蛋白(Pgp)的表达,探讨IS与多药耐药基因的关系。方法 2007年1月至2010年6月徐州医学院附属医院、徐州市儿童医院门诊及病房收治的IS患儿23例,分为2组:治疗前组、治疗超过6个月组。同期选取其他癫痫发作类型组12例、正常对照组10名。采用逆转录聚合酶链反应(RT-PCR)半定量法检测患儿外周血中MDR1基因mRNA的表达,流式细胞术检测患儿外周血Pgp表达。结果小儿外周血MDR1 mRNA与Pgp蛋白表达呈高度正相关(r=0.86,P<0.05)。治疗前组、治疗超过6个月组、其他癫痫发作类型组外周血MDR1 mRNA和Pgp蛋白表达均较正常对照组增高,且治疗前组、治疗超过6个月组MDR1基因mRNA和Pgp蛋白表达水平明显高于其他癫痫发作类型组,差异均有统计学意义(P<0.05,P<0.01)。治疗前组、治疗超过6个月组间MDR1 mRNA和Pgp蛋白表达差异无统计学意义(P>0.05)。结论 IS患儿MDR1和Pgp表达增高可能是临床耐药的重要原因,且可能为内源性耐药。

Objective To observe the expression of multiple drug resistancel （MDR1） mRNA and P-glycoprutein （P-gp） in peripheral blood, discuss the relationship between infantile spasms （IS） and MDR. Methods Use reverse transcription polymerase chain reaction （RT- PCR）to Semi-quantitatively detect the expression of M DR l gene mRNA in children＇s peripheral blood, flow cytometry to messure the expression of P-glycoprotein. The patients were divided into A group （IS not treated）, B group （IS treated over 6 months）, C group （other seizure types）and D group （healthy control group）. Results A positive correlation was found between the expression of MDR1 and P-gp （r = 0.86, P 〈 0.05）.The expression of MDR1 gene and P-gp was significantly different in four groups in peripheral blood （P 〈 0.05）.MRNA＇s expression of MDR1 gene and P-gp have increased in peripheral blood in A, B and C group. And MDR1 gene mRNA and P-gp expression level in A and B groups was significantly higher than that of C group and D group （P 〈 0.001, P 〈 0.05 ）. There was no significant difference between A and B group. Conclusion The increased expression of MDR1 P-gp in children with infantile spasms may be an important reason for clinical drug resistance.