CAJ | 학술논문

目的：通过对难治性癫痫患者外周血中多药耐药基因1（MDR1）、P 糖蛋白（P - gp）及谷胱甘肽 S 转移酶（GST - pi）的检测探讨难治性癫痫的发病机制；检测在不同发作类型、V - EEG 中癫痫样放电部位及用药方式的患者中此3项指标的水平。方法选取2012年3月—2013年3月贵州医科大学附属医院临床确诊的散发性的难治性癫痫患者31例（难治性癫痫组），另选择同期在本院接受抗癫痫药物控制良好的癫痫患者33例（治疗有效组），荧光定量法检测外周血 MDR1、GST - pi基因相对表达量，采用流式细胞术检测外周血 MDR1的表达产物P - gp的表达。结合临床特点与长程视频脑电图研究癫痫患者的发作类型、异常放电部位及用药方式，比较不同类型癫痫患者以上3项指标的表达情况。结果难治性癫痫组 MDR1、GST - pi基因相对表达量和白细胞P - gp高于治疗有效组，差异均有统计学意义（P ﹤0.01）。无论是治疗有效组还是难治性癫痫组，不同发作类型患者 MDR1、GST - pi基因相对表达量及白细胞P - gp比较，差异均无统计学意义（P ﹥0.05）。不同 V - EEG 异常放电患者 MDR1、GST - pi基因相对表达量及白细胞P - gp比较，差异均无统计学意义（P ﹥0.05）。不同用药方式患者 MDR1基因相对表达量比较，差异无统计学意义（P ﹥0.05）；不同用药方式患者GST - pi基因相对表达量和白细胞P - gp比较，差异均有统计学意义（P ﹤0.05），其中2种和3种用药方式GST - pi基因相对表达量均高于1种用药方式，3种用药方式白细胞P - gp高于1种和2种用药方式，差异均有统计学意义（P ﹤0.05）。结论癫痫患者外周血中GST - pi、P - gp或可成为难治性癫痫联合用药的耐药指标之一；癫痫患者外周血中 MDR1、GST - pi及P - gp与癫痫发作类型、癫痫样放电在 V - EEG 中的各种分布情况无明显相关性。目的：通過對難治性癲癇患者外週血中多藥耐藥基因1（MDR1）、P 糖蛋白（P - gp）及穀胱甘肽 S 轉移酶（GST - pi）的檢測探討難治性癲癇的髮病機製；檢測在不同髮作類型、V - EEG 中癲癇樣放電部位及用藥方式的患者中此3項指標的水平。方法選取2012年3月—2013年3月貴州醫科大學附屬醫院臨床確診的散髮性的難治性癲癇患者31例（難治性癲癇組），另選擇同期在本院接受抗癲癇藥物控製良好的癲癇患者33例（治療有效組），熒光定量法檢測外週血 MDR1、GST - pi基因相對錶達量，採用流式細胞術檢測外週血 MDR1的錶達產物P - gp的錶達。結閤臨床特點與長程視頻腦電圖研究癲癇患者的髮作類型、異常放電部位及用藥方式，比較不同類型癲癇患者以上3項指標的錶達情況。結果難治性癲癇組 MDR1、GST - pi基因相對錶達量和白細胞P - gp高于治療有效組，差異均有統計學意義（P ﹤0.01）。無論是治療有效組還是難治性癲癇組，不同髮作類型患者 MDR1、GST - pi基因相對錶達量及白細胞P - gp比較，差異均無統計學意義（P ﹥0.05）。不同 V - EEG 異常放電患者 MDR1、GST - pi基因相對錶達量及白細胞P - gp比較，差異均無統計學意義（P ﹥0.05）。不同用藥方式患者 MDR1基因相對錶達量比較，差異無統計學意義（P ﹥0.05）；不同用藥方式患者GST - pi基因相對錶達量和白細胞P - gp比較，差異均有統計學意義（P ﹤0.05），其中2種和3種用藥方式GST - pi基因相對錶達量均高于1種用藥方式，3種用藥方式白細胞P - gp高于1種和2種用藥方式，差異均有統計學意義（P ﹤0.05）。結論癲癇患者外週血中GST - pi、P - gp或可成為難治性癲癇聯閤用藥的耐藥指標之一；癲癇患者外週血中 MDR1、GST - pi及P - gp與癲癇髮作類型、癲癇樣放電在 V - EEG 中的各種分佈情況無明顯相關性。
목적：통과대난치성전간환자외주혈중다약내약기인1（MDR1）、P 당단백（P - gp）급곡광감태 S 전이매（GST - pi）적검측탐토난치성전간적발병궤제；검측재불동발작류형、V - EEG 중전간양방전부위급용약방식적환자중차3항지표적수평。방법선취2012년3월—2013년3월귀주의과대학부속의원림상학진적산발성적난치성전간환자31례（난치성전간조），령선택동기재본원접수항전간약물공제량호적전간환자33례（치료유효조），형광정량법검측외주혈 MDR1、GST - pi기인상대표체량，채용류식세포술검측외주혈 MDR1적표체산물P - gp적표체。결합림상특점여장정시빈뇌전도연구전간환자적발작류형、이상방전부위급용약방식，비교불동류형전간환자이상3항지표적표체정황。결과난치성전간조 MDR1、GST - pi기인상대표체량화백세포P - gp고우치료유효조，차이균유통계학의의（P ﹤0.01）。무론시치료유효조환시난치성전간조，불동발작류형환자 MDR1、GST - pi기인상대표체량급백세포P - gp비교，차이균무통계학의의（P ﹥0.05）。불동 V - EEG 이상방전환자 MDR1、GST - pi기인상대표체량급백세포P - gp비교，차이균무통계학의의（P ﹥0.05）。불동용약방식환자 MDR1기인상대표체량비교，차이무통계학의의（P ﹥0.05）；불동용약방식환자GST - pi기인상대표체량화백세포P - gp비교，차이균유통계학의의（P ﹤0.05），기중2충화3충용약방식GST - pi기인상대표체량균고우1충용약방식，3충용약방식백세포P - gp고우1충화2충용약방식，차이균유통계학의의（P ﹤0.05）。결론전간환자외주혈중GST - pi、P - gp혹가성위난치성전간연합용약적내약지표지일；전간환자외주혈중 MDR1、GST - pi급P - gp여전간발작류형、전간양방전재 V - EEG 중적각충분포정황무명현상관성。
Objective To investigate the pathogenesis of refractory epilepsy by detecting the expression of MDR1, P - gp and GST - pi in peripheral blood of patients with refractory epilepsy and to detect the expression levels of the three indexes in patients with different types of epilepsy seizure,different epileptic discharge areas shown by V - EEG and different types of medication. Methods We enrolled 31 patients who were definitely diagnosed with sporadic refractory epilepsy in the Affiliated Hospital of Guizhou Medical University from March 2012 to March 2013 as the refractory group. Another 33 epilepsy patients who were treated well by antiepileptic drug in the same period were also enrolled as the effective group. Fluorescent quantitation method was employed to detect the change of relative gene expression of MDR1 and GST - pi in peripheral blood,and flow cytometry was employed to detect the expression of P - gp,an expression product of MDR1 in peripheral blood. Comparison was made in the expression of the three indexes among patients with different types of epilepsy in combination with clinical features,types of epilepsy seizure and abnormal discharge areas shown by long - term video EEG and different medications. Results Refractory group was higher(P ﹤ 0. 01)than effective group in the gene relative expression of MDR1 and GST - pi and P - gp level of white cells. The patients with different epilepsy seizure types in two groups were no significantly different( P ﹥ 0. 05) in the gene relative expression of MDR1 and GST - pi and P - gp level of white cells. Patients with different abnormal discharge areas shown by V - EEG were not significantly different(P ﹥ 0. 05)in the gene relative expression of MDR1 and GST - pi and P - gp level of white cells. Patients with different medications were not significantly different( P ﹥ 0. 05) in the gene relative expression of MDR1;patients with different medications were significantly different( P ﹤ 0. 05) in the gene relative expression of GST - pi and P - gp level of white cells,with patients taking 2 or 3 kinds of medicine higher(P ﹤ 0. 05)than patients taking 1 kind of medicine in the gene relative expression of GST - pi and patients taking 3 kinds of medicine higher( P ﹤ 0. 05) than patients taking 1 or 2 kinds of medicine in expression of P - gp of white cells. Conclusion GST - pi and P - gp in the peripheral blood of epilepsy patients may have the potential to become drug resistance indexes of the combined drug therapy for refractory epilepsy;the levels of MDR1,GST - pi and P - gp in the peripheral blood of epilepsy patients have no obvious relevancy with the type of epilepsy seizure and the various distribution of epilepsy discharge areas shown by V - EEG.